The DOI matches its Crossref record; 300 of the 305 references it cites were found in a registry or an index; none of the 310 sources its claims cite is checked for support yet.
Reward, Addiction, Withdrawal to Nicotine
Open accessAbstract
Nicotine is the principal addictive component that drives continued tobacco use despite users' knowledge of the harmful consequences. The initiation of addiction involves the mesocorticolimbic dopamine system, which contributes to the processing of rewarding sensory stimuli during the overall shaping of successful behaviors. Acting mainly through nicotinic receptors containing the α4 and β2 subunits, often in combination with the α6 subunit, nicotine increases the firing rate and the phasic bursts by midbrain dopamine neurons. Neuroadaptations arise during chronic exposure to nicotine, producing an altered brain condition that requires the continued presence of nicotine to be maintained. When nicotine is removed, a withdrawal syndrome develops. The expression of somatic withdrawal symptoms depends mainly on the α5, α2, and β4 (and likely α3) nicotinic subunits involving the epithalamic habenular complex and its targets. Thus, nicotine taps into diverse neural systems and an array of nicotinic acetylcholine receptor (nAChR) subtypes to influence reward, addiction, and withdrawal.
Overview
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Written from the paper’s full text.
TL;DR
Nicotine drives reward and addiction mainly by acting on β2-containing nAChRs in the mesocorticolimbic dopamine system, increasing midbrain dopamine neuron firing and phasic bursts. Withdrawal depends on distinct nAChR subunits—especially α5, α2, and β4—in the habenulo-interpeduncular axis, so reward, addiction, and withdrawal are mediated by partially separate neural circuits.
Key findings
- Nicotine increases dopamine neuron firing and phasic burst activity, with tonic firing roughly 4 Hz and phasic bursts roughly 20–80 Hz; β2* nAChRs, often with α4 and/or α6, are essential for nicotine reinforcement and dopamine release.
- In mice lacking β2, nicotine does not induce phasic bursts, dopamine release, or self-administration; re-expression of β2 in the VTA, but not SNc, reinstates self-administration, and either α4 or α6 re-expression also reinstates it.
- Somatic withdrawal signs depend on α5, α2, and β4 nAChR subunits in the medial habenula/interpeduncular nucleus (MHb/IPN); mecamylamine injected into Hb/IPN precipitates withdrawal, whereas injection into VTA, hippocampus, or cortex does not.
- Withdrawal is associated with decreased extracellular dopamine in the NAc and increased dopamine output in the PFC; symptoms appear within a few hours and include irritability, anxiety, anger, difficulty concentrating, sleep disturbance, increased appetite, and weight gain.
Methods
- Narrative review synthesizing published literature on nicotinic acetylcholine receptors, mesocorticolimbic dopamine circuitry, nicotine reward, neuroadaptations, and withdrawal.
- Draws on animal models (especially mouse knockout and re-expression studies, rat electrophysiology, microdialysis, fast-scan cyclic voltammetry) and human genetic/imaging findings.
- Main analysis is qualitative integration of cited studies rather than a systematic review, meta-analysis, or new primary data.
Limitations
- Not stated in the paper: the review does not include a formal limitations section.
- Evident from the text: it is a narrative review without described systematic search criteria, inclusion/exclusion rules, or quantitative synthesis.
- Evident from the text: some conclusions are explicitly speculative, such as the proposed interpretation of SNP rs16969968 in CHRNA5 and its possible link to smoking behavior and addiction risk.
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Claims the paper makes
151 Not checked yet · 17 Own interpretation · 2 No basis given
None of the sources cited for this claim have been checked yet.
In the paper
“The epithalamic habenular complex and its targets appear to be critical for the withdrawal syndrome.”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
What the sources say
- Not checked yetcites Salas et al. 2004b
- Not checked yetcites Salas et al. 2009
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Self-stimulation of the medial forebrain bundle facilitates DA release (Garris et al. 1999, Gratton et al. 1988, Phillips et al. 1989), and DA receptor antagonists or DA neuron lesions inhibit brain self-stimulation (Fouriezos & Wise 1976, Lippa et al. 1973, Stellar & Corbett 1989).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Garris et al. 1999
- Not checked yetcites Gratton et al. 1988
- Not checked yetcites Phillips et al. 1989
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In the paper
“The effectiveness or value of rewards can be estimated by measuring the effort a subject expends on behaviors that achieve the rewarded goal (Hodos 1961, Schultz 2006).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Hodos 1961
- Not checked yetcites Schultz 2006
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The withdrawal syndrome is not mediated exactly by the same mechanisms or by the same neural circuits that initiate addiction or dependency.”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
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In the paper
“The DA efferents originating from the midbrain VTA and particularly targeting the PFC and NAc became recognized as paramount neural structures shaping reward-related behavior (Schultz et al. 1997; Wise 2004, 2009; Wise & Rompre 1989).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Schultz et al. 1997
- Not checked yetcites Wise 2004
- Not checked yetcites Wise & Rompre 1989
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In the paper
“as exemplified by lesions in the PPT reducing nicotine self-administration (Lanca et al. 2000).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Lanca et al. 2000
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, the PPT/LDT cholinergic afferents have important endogenous influences over DA neurons by acting via nAChRs (Maskos 2008, 2010).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Maskos 2008 source
- Not checked yetcites Maskos 2010
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“nicotine is the main addictive component (Benowitz 2009, Dani et al. 2009, Dani & Heinemann 1996, Mansvelder & McGehee 2002).”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
What the sources say
- Not checked yetcites Benowitz 2009
- Not checked yetcites Dani et al. 2009
- Not checked yetcites Dani & Heinemann 1996
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In the paper
“Therefore, reward mechanisms are observed across species, from insects to primates (Hodos 1961, Lau et al. 2006, McClure et al. 2007, Qin & Wheeler 2007, Wise 2006).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Hodos 1961
- Not checked yetcites Lau et al. 2006
- Not checked yetcites McClure et al. 2007
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Likewise, this DA system plays a critical role in the acquisition of behaviors that are inappropriately reinforced by psychostimulant drugs, including nicotine (Balfour 2004, Corrigall 1999, Dani et al. 2009, Dani & Heinemann 1996, Di Chiara 2000, Mansvelder & McGehee 2002).”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
What the sources say
- Not checked yetcites Balfour 2004
- Not checked yetcites Corrigall 1999
- Not checked yetcites Dani et al. 2009
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 60
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In the paper
“After chronic use of nicotine, removal of nicotine produces a withdrawal syndrome that can be relieved by nicotine replacement therapy (Dani et al. 2009, Dani & Heinemann 1996, De Biasi & Salas 2008, Di Chiara 2000, Mansvelder & McGehee 2002, Stolerman & Shoaib 1991).”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
What the sources say
- Not checked yetcites Dani et al. 2009
- Not checked yetcites Dani & Heinemann 1996
- Not checked yetcites De Biasi & Salas 2008
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Self-stimulation of the medial forebrain bundle facilitates DA release (Garris et al. 1999, Gratton et al. 1988, Phillips et al. 1989), and DA receptor antagonists or DA neuron lesions inhibit brain self-stimulation (Fouriezos & Wise 1976, Lippa et al. 1973, Stellar & Corbett 1989).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Fouriezos & Wise 1976
- Not checked yetcites Lippa et al. 1973
- Not checked yetcites Stellar & Corbett 1989
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Acting mainly via midbrain nAChRs composed of the β2 subunit in combination with the α4 and/or α6 subunits, nicotine increases the firing rate and phasic burst activity of midbrain DA neurons and elevates DA in the PFC, NAc, and other targets (Imperato et al. 1986, Grenhoff et al. 1986, Mameli-Engvall et al. 2006, Pons et al. 2008, Zhang et al. 2009b).”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
What the sources say
- Not checked yetcites Imperato et al. 1986
- Not checked yetcites Grenhoff et al. 1986
- Not checked yetcites Mameli-Engvall et al. 2006
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Rewarding stimuli promote learning of goal-directed behaviors, generate positive emotions, and subsequently stimulate repetition of those learned behaviors (Schultz 2010, Thorndike 1911).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Schultz 2010
- Not checked yetcites Thorndike 1911
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In particular, the mesocorticolimbic dopamine (DA) system plays an important role in self-stimulation and in processing environmental reward.”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
What the sources say
- Not checked yetcites Olds 1958
- Not checked yetcites Olds & Milner 1954
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Early investigations showed that the midbrain dopamine (DA) systems have an important role in the response to salient stimuli and to brain self-stimulation (Phillips & Olds 1969; Fibiger 1978, Wise 1978).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Phillips & Olds 1969
- Not checked yetcites Fibiger 1978
- Not checked yetcites Wise 1978
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The medial habenula (MHb) and one of its primary targets, the interpeduncular nucleus (IPN), richly express β4 and α5 nAChR subunits (and α2 only in the rodent IPN), which are necessary for the neuroadaptations that lead to somatic withdrawal symptoms during nicotine abstinence (Salas et al. 2004b, 2009).”
§ Reward, Addiction, Withdrawal to Nicotine > INTRODUCTION AND SUMMARY
What the sources say
- Not checked yetcites Salas et al. 2004b
- Not checked yetcites Salas et al. 2009
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The PPT/LDT cholinergic afferents boost glutamate afferent transmission via presynaptic nAChRs (Pidoplichko et al. 2004, Schilstrom et al. 2000) and provide some excitatory drive to GABA projection neurons and interneurons, mainly via β2-containing (β2*) nAChRs (Mansvelder et al. 2002, Pidoplichko et al. 2004, Pons et al. 2008).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Pidoplichko et al. 2004
- Not checked yetcites Schilstrom et al. 2000
- Not checked yetcites Mansvelder et al. 2002
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Although only ~2% of the striatal neurons are cholinergic, they have extremely dense axonal arbors that provide denser cholinergic innervation than is seen anywhere else in the brain (Butcher & Woolf 1984, Zhou et al. 2001, 2002).”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Butcher & Woolf 1984
- Not checked yetcites Zhou et al. 2001
- Not checked yetcites Zhou et al. 2002
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Addictive drugs (including nicotine) increase the basal DA concentration in the NAc shell as measured by microdialysis, but that background increase is smaller or not detected in the dorsolateral striatum (Di Chiara 1999, Pidoplichko et al. 2004, Pontieri et al. 1996, Zhang et al. 2009b).”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Di Chiara 1999
- Not checked yetcites Pidoplichko et al. 2004
- Not checked yetcites Pontieri et al. 1996
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nicotine, at the concentration obtained from tobacco, induces phasic bursts from VTA/SNc DA neurons (Figure 1b) that innervate much of the dorsal to ventral extent of the striatum (Grenhoff et al. 1986, Pidoplichko et al. 1997, Schilstrom et al. 2003, Zhang et al. 2009b), suggesting that the DA signal should be comparable throughout the striatum.”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Grenhoff et al. 1986
- Not checked yetcites Pidoplichko et al. 1997
- Not checked yetcites Schilstrom et al. 2003
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, phasic burst firing is induced by unpredicted reward or unanticipated cues that have been conditioned to a known reward (Schultz 2007b, Schultz et al. 1997).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Schultz 2007b
- Not checked yetcites Schultz et al. 1997
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Tonic firing is at a relatively low frequency (roughly 4 Hz) that generally consists of individual action potentials. Phasic firing is usually at a higher average frequency, and it includes high-frequency burst discharges (roughly 20–80 Hz) (Grace et al. 2007; Grace & Bunney 1983, 1984; Hyland et al. 2002; Robinson et al. 2004).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Grace et al. 2007
- Not checked yetcites Grace & Bunney 1983
- Not checked yetcites Hyland et al. 2002
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In the paper
“Nicotine self-administration is reinstated by re-expression of the β2 subunit in the VTA but not in the neighboring SNc (Avale et al. 2008), confirming the specific role of the VTA in reward.”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Avale et al. 2008
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, β2* nAChRs in combinations with both α4 and α6 subunits are important for the reinforcing properties of nicotine, and the α4 and α6 subunits cannot completely substitute for each other even though they are abundantly expressed in VTA neurons (Champtiaux et al. 2003, Salminen et al. 2007).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Champtiaux et al. 2003
- Not checked yetcites Salminen et al. 2007
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, local re-expression of α7 in the VTA did not reinstate self-administration in α7 −/− mice (Pons et al. 2008), consistent with the pharmacological evidence indicating that the α7 subunit does not influence chronic nicotine self-administration in trained rats (Grottick & Higgins 2000) nor nicotine-induced conditioned place preference (Stolerman et al. 2004, Walters et al. 2006).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Grottick & Higgins 2000
- Not checked yetcites Stolerman et al. 2004
- Not checked yetcites Walters et al. 2006
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Nicotinic receptors are expressed on DA neuron fibers and terminals, and the activity of those nAChRs, particularly containing the β2, α4, and α6 subunits (Pons et al. 2008), is highly regulated by ongoing striatal cholinergic interneuron discharges and dense acetylcholine esterase activity (Zhou et al. 2001, 2003).”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Pons et al. 2008
- Not checked yetcites Zhou et al. 2001
- Not checked yetcites Zhou et al. 2003
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Those DA projection target areas are involved in reinforcement (ventral striatum), learning and declarative memory (hippocampus), emotional memory (amygdala), and habit formation (dorsal striatum), as well as executive functions and working memory (PFC and orbitofrontal cortex) (Schultz W. 2007b, Laviolette 2007, Seamans & Yang 2004).”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Schultz W. 2007b
- Not checked yetcites Laviolette 2007
- Not checked yetcites Seamans & Yang 2004
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Disrupting those bursts impairs conditioned behavioral responses, diminishes the ability to learn cues about reward and salience, and disrupts the overall processing of reward (Schultz 2007b).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Schultz 2007b
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nicotine self-administration is also reinstated by the re-expression of either the α4 or the α6 nAChR subunit, consistent with the expression of α4β2 and α4α6β2 nAChRs in the VTA (Pons et al. 2008).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Pons et al. 2008
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phasic burst firing by DA neurons and the consequent downstream phasic DA signals are vital for processing reward-related information and, thus, are important for the initial phase of addiction.”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nicotine directly activates DA neurons via those and other nAChR subtypes (Pidoplichko et al. 1997), and nicotine modifies the firing modes and firing frequency of DA neurons through excitatory and inhibitory inputs and synaptic plasticity (Mameli-Engvall et al. 2006; Schilstrom et al. 2000, 2003; Zhang et al. 2009b).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Pidoplichko et al. 1997
- Not checked yetcites Mameli-Engvall et al. 2006
- Not checked yetcites Schilstrom et al. 2000
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In mice lacking the β2 nAChR subunit (β2 −/−), nicotine does not induce phasic bursts by DA neurons (Mameli-Engvall et al. 2006), nicotine does not induce DA release, and nicotine does not support self-administration (Picciotto et al. 1998).”
§ Reward, Addiction, Withdrawal to Nicotine > REWARD AND INITIATION OF ADDICTION
What the sources say
- Not checked yetcites Mameli-Engvall et al. 2006
- Not checked yetcites Picciotto et al. 1998
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Measured in vivo from the VTA, nicotine administration to a rat causes (some) DA neurons to fire at a higher rate and to fire more and longer bursts (Figure 1).”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The details of the DA signaling change in both anatomical areas, but as judged by the area under the curves (Figure 3a,b), the data suggest that the background DA concentration would increase in the NAc shell and not the dorsal striatum (Zhang et al. 2009b).”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Zhang et al. 2009b
hedged- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“However, when nicotine is added to striatal brain slices, a significant proportion of presynaptic and axonal nAChRs is desensitized. As a consequence, low-frequency, tonic DA release is inhibited (Rice & Cragg 2004, Zhang & Sulzer 2004, Zhou et al. 2001), but phasic DA release is regulated differently, such that phasic bursts induce large DA signals (Cragg 2003; Rice & Cragg 2004; Zhang et al. 200”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Rice & Cragg 2004
- Not checked yetcites Zhang & Sulzer 2004
- Not checked yetcites Zhou et al. 2001
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the NAc shell, phasic burst discharges produce a greater increase in DA release than in the dorsal striatum, where the DA release from a single-pulse stimulus is comparable to the release from a phasic-burst stimulus.”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Zhang et al. 2009a
- Not checked yetcites Zhang et al. 2009b
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Reward omission induces phasic inhibition of VTA neurons (Schultz 2007a,b), and aversive stimuli excite ventral (Brischoux et al. 2009) and inhibit dorsal (Ungless et al. 2004) VTA neurons.”
§ Reward, Addiction, Withdrawal to Nicotine > AVERSIVE SENSORY SIGNALING IN THE MESOCORTICOLIMBIC SYSTEM
What the sources say
- Not checked yetcites Brischoux et al. 2009
- Not checked yetcites Ungless et al. 2004
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“DA axon terminals in the dorsolateral striatum and NAc shell respond differently to incoming action potentials, consistent with phasic bursts inducing a greater increase of DA release in the NAc shell (Cragg 2003; Rice & Cragg 2004; Zhang et al. 2009a,b; Zhang & Sulzer 2004), which has a more important role in mediating the rewarding properties of nicotine that drive the early phases of addiction.”
§ Reward, Addiction, Withdrawal to Nicotine > DOWNSTREAM FROM DOPAMINE NEURON PHASIC BURSTS
What the sources say
- Not checked yetcites Cragg 2003
- Not checked yetcites Rice & Cragg 2004
- Not checked yetcites Zhang et al. 2009a
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As in the LHb, RMTg neurons are phasically activated by aversive stimuli and inhibited by natural rewards such as food or reward-predictive stimuli, and conversely, RMTg neurons are stimulated by aversive stimuli (Jhou et al. 2009b).”
§ Reward, Addiction, Withdrawal to Nicotine > AVERSIVE SENSORY SIGNALING IN THE MESOCORTICOLIMBIC SYSTEM
What the sources say
- Not checked yetcites Jhou et al. 2009b
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Owing to afferents mediating sensory input, NAc neurons decrease their firing to appetitive stimuli and increase their firing to aversive stimuli (Roitman et al. 2005).”
§ Reward, Addiction, Withdrawal to Nicotine > AVERSIVE SENSORY SIGNALING IN THE MESOCORTICOLIMBIC SYSTEM
What the sources say
- Not checked yetcites Roitman et al. 2005
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Nicotine exposure also increases high-affinity DA D2 receptors in the NAc (Novak et al. 2010), an effect, also produced by cocaine, that causes DA hypersensitivity (Briand et al. 2008, Grigoriadis & Seeman 1986).”
§ Reward, Addiction, Withdrawal to Nicotine > NICOTINE-INDUCED NEUROADAPTATIONS
What the sources say
- Not checked yetcites Novak et al. 2010
- Not checked yetcites Briand et al. 2008
- Not checked yetcites Grigoriadis & Seeman 1986
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the NAc of rats, intraoral sucrose (i.e., rewarding) infusion increased DA levels, whereas quinine (i.e., aversive) infusion decreased DA levels (Roitman et al. 2008).”
§ Reward, Addiction, Withdrawal to Nicotine > AVERSIVE SENSORY SIGNALING IN THE MESOCORTICOLIMBIC SYSTEM
What the sources say
- Not checked yetcites Roitman et al. 2008
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nicotinic receptor upregulation differs among the diverse subtypes, varies among brain regions for the same nAChR subtype, and depends on the contingency of nicotine administration (Gaimarri et al. 2007, Marks et al. 1983, McCallum et al. 2006, Metaxas et al. 2010, Nguyen et al. 2004, Pauly et al. 1996, Schwartz & Kellar 1983).”
§ Reward, Addiction, Withdrawal to Nicotine > NICOTINE-INDUCED NEUROADAPTATIONS
What the sources say
- Not checked yetcites Gaimarri et al. 2007
- Not checked yetcites Marks et al. 1983 source
- Not checked yetcites McCallum et al. 2006
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Because nicotine is not hydrolyzed by acetylcholine esterase, as ACh is, nicotine’s long-lasting presence favors excessive nAChR desensitization. The homeostatic response to desensitized (turned-off) receptors is upregulation (Dani & Heinemann 1996, Fenster et al. 1999, Picciotto et al. 2008).”
§ Reward, Addiction, Withdrawal to Nicotine > NICOTINE-INDUCED NEUROADAPTATIONS
What the sources say
- Not checked yetcites Dani & Heinemann 1996
- Not checked yetcites Fenster et al. 1999
- Not checked yetcites Picciotto et al. 2008
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The RMTg sends GABAergic projections to the VTA and SNc and inhibits DA cells (Ikemoto 2010, Jhou et al. 2009a).”
§ Reward, Addiction, Withdrawal to Nicotine > AVERSIVE SENSORY SIGNALING IN THE MESOCORTICOLIMBIC SYSTEM
What the sources say
- Not checked yetcites Ikemoto 2010
- Not checked yetcites Jhou et al. 2009a
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The IPN, in turn, sends projections to the serotonergic raphé nuclei and to the dopaminergic VTA (Groenewegen et al. 1986, Klemm 2004, Montone et al. 1988).”
§ Reward, Addiction, Withdrawal to Nicotine > AVERSIVE SENSORY SIGNALING IN THE MESOCORTICOLIMBIC SYSTEM
What the sources say
- Not checked yetcites Groenewegen et al. 1986
- Not checked yetcites Klemm 2004
- Not checked yetcites Montone et al. 1988
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The emergence of negative affective symptoms such as dysphoria, anxiety, and irritability (Koob & Le Moal 2001) and, to a lesser extent, the somatic manifestations of withdrawal, signal dependency and underlie drug-seeking behavior (Koob & Le Moal 2005, Koob & Volkow 2009).”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
What the sources say
- Not checked yetcites Koob & Le Moal 2005
- Not checked yetcites Koob & Volkow 2009
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Other quantifiable manifestations include reduced heart rates, altered neurohormonal profiles, disrupted electroencephalographic theta power, and perturbations of learned behaviors (Buchhalter et al. 2008, Koob & Le Moal 2005).”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
What the sources say
- Not checked yetcites Buchhalter et al. 2008
- Not checked yetcites Koob & Le Moal 2005
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Powerful cravings also accompany withdrawal, and they may be precipitated by drug-reinforced memories, such as the sight of a cigarette and the place associated with smoking (Dalley & Everitt 2009, Dani & Montague 2007, Shiffman et al. 2002, Smolka et al. 2005, Volkow et al. 2002).”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
What the sources say
- Not checked yetcites Dalley & Everitt 2009
- Not checked yetcites Dani & Montague 2007
- Not checked yetcites Shiffman et al. 2002
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Nicotine cessation increases the levels of prodynorphin mRNA in NAc dynorphinergic neurons, possibly as a compensatory mechanism to increased dynorphinergic tone (Isola et al. 2008).”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
What the sources say
- Not checked yetcites Isola et al. 2008
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
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In the paper
“In particular, dynorphins decrease and enkephalins increase the release of DA (Devine et al. 1993; Di Chiara & Imperato 1988; Longoni et al. 1991; Pentney & Gratton 1991; Spanagel et al. 1990a,b, 1992).”
§ Reward, Addiction, Withdrawal to Nicotine > NICOTINE-INDUCED NEUROADAPTATIONS
What the sources say
- Not checked yetcites Devine et al. 1993 source
- Not checked yetcites Di Chiara & Imperato 1988
- Not checked yetcites Longoni et al. 1991
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The overall neuroadaptations contribute to the mechanisms that maintain nicotine consumption, including mechanisms underlying associative learning (Tang & Dani, 2009), and they also participate in the nicotine-withdrawal syndrome (De Biasi & Salas 2008, Hadjiconstantinou & Neff 2010).”
§ Reward, Addiction, Withdrawal to Nicotine > NICOTINE-INDUCED NEUROADAPTATIONS
What the sources say
- Not checked yetcites Tang & Dani, 2009
- Not checked yetcites De Biasi & Salas 2008
- Not checked yetcites Hadjiconstantinou & Neff 2010
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The endogenous opioid system influences positive and negative motivational and affective states (Steiner & Gerfen 1998) and participates in the behavioral effects of several addictive drugs, including nicotine (Berrendero et al. 2005, Hadjiconstantinou & Neff 2010, Trigo et al. 2009).”
§ Reward, Addiction, Withdrawal to Nicotine > NICOTINE-INDUCED NEUROADAPTATIONS
What the sources say
- Not checked yetcites Steiner & Gerfen 1998
- Not checked yetcites Berrendero et al. 2005
- Not checked yetcites Hadjiconstantinou & Neff 2010
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This phenomenon is similar to the anxiety reported by humans experiencing nicotine abstinence and suggests that the sensitivity to anxiety influences the degree of withdrawal signs.”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“During withdrawal, the NAc displays a DA deficit, whereas the PFC has an increase in DA output (Carboni et al. 2000).”
§ Reward, Addiction, Withdrawal to Nicotine > MOLECULAR MECHANISMS OF WITHDRAWAL
What the sources say
- Not checked yetcites Carboni et al. 2000
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Withdrawal reflects the abrupt disruption of the equilibrium maintained in the presence of nicotine, and withdrawal triggers new neuroadaptations that counteract the negative state.”
§ Reward, Addiction, Withdrawal to Nicotine > MOLECULAR MECHANISMS OF WITHDRAWAL
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mecamylamine, which has a slightly higher affinity for α3β4* nAChRs than for β2* receptors, is the best antagonist at precipitating nicotine withdrawal (Damaj et al. 2003).”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
What the sources say
- Not checked yetcites Damaj et al. 2003
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nicotine abstinence is accompanied by increased DA uptake into synaptosomes and elevated DA transporters (DATs) in the SNc/VTA (Hadjiconstantinou & Neff 2010, Rahman et al. 2004).”
§ Reward, Addiction, Withdrawal to Nicotine > MOLECULAR MECHANISMS OF WITHDRAWAL
What the sources say
- Not checked yetcites Hadjiconstantinou & Neff 2010
- Not checked yetcites Rahman et al. 2004
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Anhedonia, conditioned place aversion, anxiety-related behavior, and conditioned fear are four major affective manifestations of nicotine withdrawal.”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Because enhanced DA transmission in the PFC occurs during stressful and aversive stimuli and is implicated in anxiety”
§ Reward, Addiction, Withdrawal to Nicotine > MOLECULAR MECHANISMS OF WITHDRAWAL
What the sources say
- Not checked yetcites Bradberry et al. 1991
- Not checked yetcites Broersen et al. 2000
- Not checked yetcites Inglis & Moghaddam 1999
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Buproprion may aid smoking cessation, in part, by normalizing NAc DA levels, and those DA levels may in turn attenuate anhedonia and somatic withdrawal signs (Cryan et al. 2003, Paterson & Markou 2007).”
§ Reward, Addiction, Withdrawal to Nicotine > MOLECULAR MECHANISMS OF WITHDRAWAL
What the sources say
- Not checked yetcites Cryan et al. 2003
- Not checked yetcites Paterson & Markou 2007
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Rests on an assumption: Bupropion inhibits nAChRs and is mainly a norepinephrine/dopamine reuptake blocker.
In the paper
“as nicotine withdrawal produces deficits in contextual fear conditioning and affects the acquisition of learned responses (Portugal et al. 2008).”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
What the sources say
- Not checked yetcites Portugal et al. 2008
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both spontaneous (Epping-Jordan et al. 1998, Harrison et al. 2001) and mecamylamine-precipitated (Watkins et al. 2000) nicotine withdrawal induce increases in self-stimulation thresholds.”
§ Reward, Addiction, Withdrawal to Nicotine > BEHAVIORAL MANIFESTATIONS OF NICOTINE WITHDRAWAL
What the sources say
- Not checked yetcites Epping-Jordan et al. 1998
- Not checked yetcites Harrison et al. 2001
- Not checked yetcites Watkins et al. 2000 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Absence of β4 abolishes the somatic signs of withdrawal precipitated by systemic injection of mecamylamine (Salas et al. 2004b) and prevents withdrawal-induced hyperalgesia (Salas et al. 2004b).”
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
What the sources say
- Not checked yetcites Salas et al. 2004b
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Third, a derivative of the alkaloid ibogaine, 18-methoxycoronaridine (18-MC) (Vastag 2005), is a potent antagonist of β4* nAChRs (Glick et al. 2002) with significant antiaddictive properties (Maisonneuve & Glick 2003).”
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
What the sources say
- Not checked yetcites Glick et al. 2002
- Not checked yetcites Maisonneuve & Glick 2003
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The primary circuits underlying this exquisitely regulated dosing are mainly the mesocorticolimbic DA system and the epithalamic habenular circuits: One supports the rising arm, the other the falling arm of the inverted U dose-response curve.”
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Smokers regulate puffing and inhalation depth to achieve the most desirable nicotine dose at the top of the inverted U dose-response curve.
In the paper
“In animal models, 18-MC reduced self-administration of nicotine, morphine, cocaine, and methamphetamine; reduced oral intake of alcohol and nicotine; and decreased signs of opioid withdrawal (Maisonneuve & Glick 2003).”
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
What the sources say
- Not checked yetcites Maisonneuve & Glick 2003
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Attenuation of nicotine-induced seizure is also present in mice heterozygous for the α3 subunit, which is found in the same gene cluster that contains α5 and β4 (Boulter et al. 1990, Salas et al. 2004a).”
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
What the sources say
- Not checked yetcites Boulter et al. 1990 source
- Not checked yetcites Salas et al. 2004a
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent findings on the influence of gene variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on nicotine addiction (Bierut et al. 2008, Thorgeirsson et al. 2008) show that a single nucleotide polymorphism (SNP) within CHRNA5, rs16969968, seems to correlate with nicotine dependency risk, heavy smoking, and the pleasurable sensation produced by a cigarette (Berrettini et al. 2008, Bierut et al. 2008,”
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
What the sources say
- Not checked yetcites Berrettini et al. 2008
- Not checked yetcites Bierut et al. 2008
- Not checked yetcites Saccone et al. 2007
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
No mRNA encoding nAChR subunits can be detected in the lateral habenula by in situ hybridization.
“and no mRNA encoding for nAChR subunits can be detected in the LHb by in situ hybridization techniques.”
The paper relies on this without support.
Smokers regulate puffing and inhalation depth to achieve the most desirable nicotine dose at the top of the inverted U dose-response curve.
“Smokers finely control nicotine intake by regulating how they puff on a cigarette and how deeply they inhale. In that way, they achieve the most desirable nicotine dose, at the top of the inverted U dose-response curve.”
The paper relies on this without support.
Bupropion inhibits nAChRs and is mainly a norepinephrine/dopamine reuptake blocker.
“Although buproprion inhibits nAChRs, it is mainly a norepinephrine/DA re-uptake blocker.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Therefore, during the withdrawal period, phasic DA neuron activity of the kind induced by nicotine (9, 30) re-exposure induces DA signals that may make smokers in the withdrawal period more vulnerable to the reinforcing influence of nicotine (2).”
From Withdrawal from Chronic Nicotine Exposure Alters Dopamine Signaling Dynamics in the Nucleus Accumbens (2012) · cites this paper as [2]
Experimental — accuracy not yet measuredIn the citing paper
“The role of the DAergic system (in particular the mesocorticolimbic pathway) in drug addiction derives from DA’s ability to modulate many of the limbic and cortical sites involved in goal-directed behavior (Fig. 1) [18, 28–31].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [18]
In the citing paper
“Studies conducted in recent years have identified the LHb as a source of anti-reward signals that plays an important role in determining the reward-related activity of DA neurons [18, 30, 68–70].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [18]
In the citing paper
“Nicotine follows an inverted U-shaped dose-response curve [18, 60], and smokers titrate their nicotine intake to experience the rewarding while avoiding the aversive effects produced by high nicotine doses [61–64].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [18]
In the citing paper
“as well as the habenulo-interpeduncular pathway, which has been implicated in the addictive effects of smoking (Dani and Bertrand, 2007;De Biasi and Dani, 2011).”
From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as De Biasi and Dani, 2011
In the citing paper
“Another critical site of action would be the mesolimbic dopamine system, which is a major contributor to reward function and addiction”
From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as De Biasi and Dani, 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
“Because the nAChR subunits comprised in the CHRNA5-CHRNA3-CHRNB4 reduce the aversive effects of nicotine and drive its consumption”
§ Reward, Addiction, Withdrawal to Nicotine > DISTINCT NICOTINIC RECEPTOR SUBTYPES MEDIATE WITHDRAWAL
“people with SNP rs16969968 smoke more and become addicted at a younger age because they lack sufficient functional α5* nAChRs. The presence of fewer aversive effects (even at higher nicotine doses) during the initial contact with the drug would promote the hedonic drive”
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“…nicotine use is the subtype-specific upregulation of nAChRs (Buisson & Bertrand 2001; Changeux et al. 1984; Dani & Heinemann 1996; Flores et al. 1997; Mansvelder et al. 2002; Marks et al. 1983, 1992; Perry et al. 1999; Rezvani et al. 2007, 2009; Rowell & Wonnacott 1990; Schwartz & Kellar 1983).”
BackgroundRole of dopamine in the behavioural actions of nicotine related to addiction
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“Likewise, this DA system plays a critical role in the acquisition of behaviors that are inappropriately reinforced by psychostimulant drugs, including nicotine (Balfour 2004, Corrigall 1999, Dani et al. 2009, Dani & Heinemann 1996, Di Chiara 2000, Mansvelder & McGehee 2002).”
BackgroundJhou, T. C., Fields, H. L., Baxter, M. G., Saper, C. B., & Holland, P. C. (2009) · Neuron · doi:10.1016/j.neuron.2009.02.001 · Cited by 696 · cited 2×
“As in the LHb, RMTg neurons are phasically activated by aversive stimuli and inhibited by natural rewards such as food or reward-predictive stimuli, and conversely, RMTg neurons are stimulated by aversive stimuli (Jhou et al. 2009b).”
BackgroundNicotine preferentially stimulates dopamine release in the limbic system of freely moving rats
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“…in combination with the α4 and/or α6 subunits, nicotine increases the firing rate and phasic burst activity of midbrain DA neurons and elevates DA in the PFC, NAc, and other targets (Imperato et al. 1986, Grenhoff et al. 1986, Mameli-Engvall et al. 2006, Pons et al. 2008, Zhang et al. 2009b).”
BackgroundNicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization
Tapper, A. R., McKinney, S. L., Nashmi, R., Schwarz, J., Deshpande, P., Labarca, C., Whiteaker, P., Marks, M. J., Collins, A. C., & Lester, H. A. (2004) · Science · doi:10.1126/science.1099420 · Cited by 686 · cited 1×
“In the midbrain, nAChRs comprising the β2 nAChR subunit in combination with α4 and/or α6 subunits are essential for nicotine-induced reinforcement and the DA signal (Drenan et al. 2010, Mameli-Engvall et al. 2006, Picciotto et al. 1998, Pons et al. 2008, Tapper et al. 2004).”
BackgroundGonon, F. G. (1988) · Neuroscience · doi:10.1016/0306-4522(88)90307-7 · Cited by 676 · cited 1×
“The phasic burst firing induced by nicotine causes greater extracellular DA release compared with tonic, single-spike firing (Floresco et al. 2003, Gonon 1988, Grace 1991, Zhang et al. 2009b).”
BackgroundDramatic decreases in brain reward function during nicotine withdrawal
Epping-Jordan, M. P., Watkins, S. S., Koob, G. F., & Markou, A. (1998) · Nature · doi:10.1038/30001 · Cited by 674 · cited 1×
“Both spontaneous (Epping-Jordan et al. 1998, Harrison et al. 2001) and mecamylamine-precipitated (Watkins et al. 2000) nicotine withdrawal induce increases in self-stimulation thresholds.”
BackgroundKlink, R., d'Exaerde, A. D. K., Zoli, M., & Changeux, J.-P. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01452.2001 · Cited by 674 · cited 2×
“The midbrain DA area expresses diverse nAChR subtypes (Grady et al. 2010, Klink et al. 2001, Pidoplichko et al. 1997, Wooltorton et al. 2003) and receives afferent cholinergic innervation from the nearby pedunculopontine tegmentum (PPT) and the laterodorsal tegmentum (LDT), which are a loose…”
BackgroundHabenular α5 nicotinic receptor subunit signalling controls nicotine intake
Fowler, C. D., Lu, Q., Johnson, P. M., Marks, M. J., & Kenny, P. J. (2011) · Nature · doi:10.1038/nature09797 · Cited by 663 · cited 1×
“This result suggests that α5-containing nAChRs in the MHb are key to controlling the amounts of nicotine self-administered (Fowler et al. 2011).”
BackgroundDopamine signals for reward value and risk: basic and recent data
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“This nonsynonymous SNP, located in the second intracellular loop of the α5 subunit, leads to a reduction in receptor function (Bierut et al. 2008).”
BackgroundMortality from smoking worldwide
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“…nucleus INTRODUCTION AND SUMMARY Tobacco use is the leading cause of preventable death in developed countries (Benowitz 2008, Mathers & Loncar 2006, Peto et al. 1996), and nicotine is the main addictive component (Benowitz 2009, Dani et al. 2009, Dani & Heinemann 1996, Mansvelder & McGehee 2002).”
BackgroundAcetylcholine Receptor: An Allosteric Protein
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“…most direct and important neuroadaptations induced by chronic nicotine use is the subtype-specific upregulation of nAChRs (Buisson & Bertrand 2001; Changeux et al. 1984; Dani & Heinemann 1996; Flores et al. 1997; Mansvelder et al. 2002; Marks et al. 1983, 1992; Perry et al. 1999; Rezvani et al.…”
BackgroundDrug addiction as dopamine-dependent associative learning disorder
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“Addictive drugs (including nicotine) increase the basal DA concentration in the NAc shell as measured by microdialysis, but that background increase is smaller or not detected in the dorsolateral striatum (Di Chiara 1999, Pidoplichko et al. 2004, Pontieri et al. 1996, Zhang et al. 2009b).”
BackgroundMolecular and cellular aspects of nicotine abuse
Dani, J. A., & Heinemann, S. (1996) · Neuron · doi:10.1016/s0896-6273(00)80112-9 · Cited by 605
Self-citationNicotine amplifies reward-related dopamine signals in striatum
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“Direct measures of DA release using fast-scan cyclic voltammetry indicate that the transfer function relating DA neuron activity and DA release differs in those (and likely other) locations (Figure 2) (Cragg 2003, Rice & Cragg 2004, Zhang et al. 2009a, Zhang & Sulzer 2004, Zhou et al. 2001).”
BackgroundMethodInfluentialEndogenous nicotinic cholinergic activity regulates dopamine release in the striatum
Zhou, F.-M., Liang, Y., & Dani, J. A. (2001) · Nature Neuroscience · doi:10.1038/nn769 · Cited by 585 · cited 6×
“Although only ~2% of the striatal neurons are cholinergic, they have extremely dense axonal arbors that provide denser cholinergic innervation than is seen anywhere else in the brain (Butcher & Woolf 1984, Zhou et al. 2001, 2002).”
BackgroundMethodInfluentialSelf-citationNicotine reinforcement and cognition restored by targeted expression of nicotinic receptors
Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., et al. (2005) · Nature · doi:10.1038/nature03694 · Cited by 566 · cited 3×
“Despite these potent effects of nicotine in the striatum, it is the nAChRs and nicotinic mechanisms within and impinging on the midbrain DA centers that are required for the addictive drive of nicotine (Mameli-Engvall et al. 2006, Maskos et al. 2005, Pons et al. 2008).”
BackgroundNicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment
Marks, M., Pauly, Jr., Gross, S., Deneris, E., Hermans-Borgmeyer, I., Heinemann, S., & Collins, A. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02765.1992 · Cited by 551 · cited 1×
“…nicotine use is the subtype-specific upregulation of nAChRs (Buisson & Bertrand 2001; Changeux et al. 1984; Dani & Heinemann 1996; Flores et al. 1997; Mansvelder et al. 2002; Marks et al. 1983, 1992; Perry et al. 1999; Rezvani et al. 2007, 2009; Rowell & Wonnacott 1990; Schwartz & Kellar 1983).”
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“In particular, dynorphins decrease and enkephalins increase the release of DA (Devine et al. 1993; Di Chiara & Imperato 1988; Longoni et al. 1991; Pentney & Gratton 1991; Spanagel et al. 1990a,b, 1992).”
BackgroundSutherland, R. J. (1982) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(82)90003-3 · Cited by 537 · cited 1×
“…striatum via the stria medullaris thalami and sends projections to the IPN, the VTA, the SNc, the medial raphe complex, the locus coeruleus, and the periaqueductal gray (Geisler et al. 2008; Greatrex & Phillipson 1982; Herkenham & Nauta 1977, 1979; Kim & Chang 2005; Scheibel 1997; Sutherland 1982).”
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“This phenomenon is also observed during ethanol, morphine, cocaine, and amphetamine withdrawal (Rossetti et al. 1992, Weiss et al. 1992) and is a trigger of the withdrawal syndrome.”
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“…accumbens; habenula; interpeduncular nucleus INTRODUCTION AND SUMMARY Tobacco use is the leading cause of preventable death in developed countries (Benowitz 2008, Mathers & Loncar 2006, Peto et al. 1996), and nicotine is the main addictive component (Benowitz 2009, Dani et al. 2009, Dani &…”
BackgroundVolkow, N. (2002) · Neurobiology of Learning and Memory · doi:10.1006/nlme.2002.4099 · Cited by 514
Champtiaux, N., Gotti, C., Cordero‐Erausquin, M., David, D. J. P., Przybylski, C., Léna, C., Clementi, F., Moretti, M., Rossi, F., Novère, N. G. L., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07820.2003 · Cited by 512 · cited 1×
“Thus, β2* nAChRs in combinations with both α4 and α6 subunits are important for the reinforcing properties of nicotine, and the α4 and α6 subunits cannot completely substitute for each other even though they are abundantly expressed in VTA neurons (Champtiaux et al. 2003, Salminen et al. 2007).”
BackgroundJhou, T. C., Geisler, S., Marinelli, M., Degarmo, B. A., & Zahm, D. S. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21891 · Cited by 503 · cited 2×
“As in the LHb, RMTg neurons are phasically activated by aversive stimuli and inhibited by natural rewards such as food or reward-predictive stimuli, and conversely, RMTg neurons are stimulated by aversive stimuli (Jhou et al. 2009b).”
BackgroundRoles for nigrostriatal—not just mesocorticolimbic—dopamine in reward and addiction
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“Therefore, reward mechanisms are observed across species, from insects to primates (Hodos 1961, Lau et al. 2006, McClure et al. 2007, Qin & Wheeler 2007, Wise 2006).”
BackgroundFiring modes of midbrain dopamine cells in the freely moving rat
Hyland, B. I., Reynolds, J. N. J., HAY, J. G., Perk, C. G., & Miller, R. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00267-1 · Cited by 487 · cited 1×
“Phasic firing is usually at a higher average frequency, and it includes high-frequency burst discharges (roughly 20–80 Hz) (Grace et al. 2007; Grace & Bunney 1983, 1984; Hyland et al. 2002; Robinson et al. 2004).”
BackgroundUllsperger, M., & von Cramon, D. Y. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-10-04308.2003 · Cited by 484
Nicotinic Cholinergic Receptor Binding Sites in the Brain: Regulation in Vivo
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“…nicotine use is the subtype-specific upregulation of nAChRs (Buisson & Bertrand 2001; Changeux et al. 1984; Dani & Heinemann 1996; Flores et al. 1997; Mansvelder et al. 2002; Marks et al. 1983, 1992; Perry et al. 1999; Rezvani et al. 2007, 2009; Rowell & Wonnacott 1990; Schwartz & Kellar 1983).”
Backgroundα-5/α-3 nicotinic receptor subunit alleles increase risk for heavy smoking
Berrettini, W., Yuan, X., Tozzi, F., Song, K., Francks, C., Chilcoat, H., Waterworth, D., Muglia, P., & Mooser, V (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002154 · Cited by 465 · cited 1×
“…al. 2008) show that a single nucleotide polymorphism (SNP) within CHRNA5, rs16969968, seems to correlate with nicotine dependency risk, heavy smoking, and the pleasurable sensation produced by a cigarette (Berrettini et al. 2008, Bierut et al. 2008, Saccone et al. 2007, Thorgeirsson et al. 2008).”
BackgroundCholinergic interneuron characteristics and nicotinic properties in the striatum
Zhou, F., Wilson, C. J., & Dani, J. A. (2002) · Journal of Neurobiology · doi:10.1002/neu.10150 · Cited by 465 · cited 1×
“Although only ~2% of the striatal neurons are cholinergic, they have extremely dense axonal arbors that provide denser cholinergic innervation than is seen anywhere else in the brain (Butcher & Woolf 1984, Zhou et al. 2001, 2002).”
BackgroundSelf-citationEffects of chronic nicotine infusion on tolerance development and nicotinic receptors
Marks, M. J., Burch, J. B., & Collins, A. C. (1983) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21831-6 · Cited by 464 · cited 2×
“…nicotine use is the subtype-specific upregulation of nAChRs (Buisson & Bertrand 2001; Changeux et al. 1984; Dani & Heinemann 1996; Flores et al. 1997; Mansvelder et al. 2002; Marks et al. 1983, 1992; Perry et al. 1999; Rezvani et al. 2007, 2009; Rowell & Wonnacott 1990; Schwartz & Kellar 1983).”
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“The homeostatic response to desensitized (turned-off) receptors is upregulation (Dani & Heinemann 1996, Fenster et al. 1999, Picciotto et al. 2008).”
BackgroundBrain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory
Ikemoto, S. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.02.001 · Cited by 454 · cited 3×
“Aversive, negative sensory input is processed by the habenular complex, an epithalamic structure involved in fear, anxiety, depression, and stress (Geisler et al. 2008, Ikemoto 2010, Winter et al. 2010).”
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“Owing to afferents mediating sensory input, NAc neurons decrease their firing to appetitive stimuli and increase their firing to aversive stimuli (Roitman et al. 2005).”
BackgroundCellular and synaptic mechanisms of nicotine addiction
Mansvelder, H. D., & McGehee, D. S. (2002) · Journal of Neurobiology · doi:10.1002/neu.10148 · Cited by 450 · cited 3×
“Likewise, this DA system plays a critical role in the acquisition of behaviors that are inappropriately reinforced by psychostimulant drugs, including nicotine (Balfour 2004, Corrigall 1999, Dani et al. 2009, Dani & Heinemann 1996, Di Chiara 2000, Mansvelder & McGehee 2002).”
BackgroundRole of brain dopamine in food reward and reinforcement
Wise, R. A. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1854 · Cited by 436 · cited 1×
“The DA efferents originating from the midbrain VTA and particularly targeting the PFC and NAc became recognized as paramount neural structures shaping reward-related behavior (Schultz et al. 1997; Wise 2004, 2009; Wise & Rompre 1989).”
BackgroundChristoph, G., Leonzio, R., & Wilcox, K. (1986) · The Journal of Neuroscience · doi:10.1523/jneurosci.06-03-00613.1986 · Cited by 418 · cited 1×
“Furthermore, electrical stimulation of the LHb inhibits most DA neurons (Christoph et al. 1986, Ji & Shepard 2007, Matsumoto & Hikosaka 2007).”
BackgroundImmediate antecedents of cigarette smoking: An analysis from ecological momentary assessment.
Shiffman, S., Gwaltney, C. J., Balabanis, M. H., Liu, K. S., Paty, J. A., Kassel, J. D., Hickcox, M., & Gnys, M. (2002) · Journal of Abnormal Psychology · doi:10.1037//0021-843x.111.4.531 · Cited by 405 · cited 1×
“…M anuscript Powerful cravings also accompany withdrawal, and they may be precipitated by drugreinforced memories, such as the sight of a cigarette and the place associated with smoking (Dalley & Everitt 2009, Dani & Montague 2007, Shiffman et al. 2002, Smolka et al. 2005, Volkow et al. 2002).”
BackgroundOlds, J. (1958) · Science · doi:10.1126/science.127.3294.315 · Cited by 404
Nicotinic effects on the firing pattern of midbrain dopamine neurons
GRENHOFF, J., ASTON‐JONES, G., & SVENSSON, T. H. (1986) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1986.tb07988.x · Cited by 399 · cited 4×
“…from tobacco, induces phasic bursts from VTA/SNc DA neurons (Figure 1b) that innervate much of the dorsal to ventral extent of the striatum (Grenhoff et al. 1986, Pidoplichko et al. 1997, Schilstrom et al. 2003, Zhang et al. 2009b), suggesting that the DA signal should be comparable…”
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“Furthermore, electrical stimulation of the LHb inhibits most DA neurons (Christoph et al. 1986, Ji & Shepard 2007, Matsumoto & Hikosaka 2007).”
BackgroundElectrophysiological Characterization of GABAergic Neurons in the Ventral Tegmental Area
Steffensen, S. C., Svingos, A. L., Pickel, V. M., & Henriksen, S. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-19-08003.1998 · Cited by 388 · cited 1×
“Diverse nAChR subtypes are expressed on DA, GABA, and Glu neurons of the midbrain, and nAChRs are expressed on afferent projections arriving from diverse areas, including the cortex, the PPT/LDT, and the NAc (Kalivas 1993, Steffensen et al. 1998, Walaas & Fonnum 1980).”
BackgroundDevine, D. P., Leone, P., Pocock, D., & Wise, R. A. (1993) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39324-9 · Cited by 382 · cited 1×
“In particular, dynorphins decrease and enkephalins increase the release of DA (Devine et al. 1993; Di Chiara & Imperato 1988; Longoni et al. 1991; Pentney & Gratton 1991; Spanagel et al. 1990a,b, 1992).”
BackgroundIMAGING VALUATION MODELS IN HUMAN CHOICE
Montague, P. R., King‐Casas, B., & Cohen, J. D. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112903 · Cited by 382 · cited 1×
“For humans, rewards can be more complex and abstract than food and sex and can take the form of monetary, aesthetic, cognitive, or social stimuli (Montague et al. 2006, O’Doherty et al. 2001).”
BackgroundNicotine addiction and comorbidity with alcohol abuse and mental illness
Dani, J. A., & Harris, R. A. (2005) · Nature Neuroscience · doi:10.1038/nn1580 · Cited by 382 · cited 2×
“…mechanistic actions underlie nicotine’s ability to enhance reward from brain stimulation, reinforce conditioned place preference, and support self-administration (Corrigall 1999, Dani et al. 2009, Dani & Harris 2005, Mameli-Engvall et al. 2006, Picciotto et al. 1998, Stolerman & Shoaib 1991).”
BackgroundSelf-citationSingle-neuron responses to emotional visual stimuli recorded in human ventral prefrontal cortex
Kawasaki, H., Adolphs, R., Kaufman, O., Damásio, H., Damásio, A. R., Granner, M. A., Bakken, H. E., Hori, T., & Howard, M. A. (2001) · Nature Neuroscience · doi:10.1038/82850 · Cited by 367 · cited 1×
“…in the PFC occurs during stressful and aversive stimuli and is implicated in anxiety, the elevated PFC DA during nicotine withdrawal may contribute to the aversive manifestations (Bradberry et al. 1991, Broersen et al. 2000, Inglis & Moghaddam 1999, Kawasaki et al. 2001, Thierry et al. 1976).”
BackgroundRole of dynorphin and enkephalin in the regulation of striatal output pathways and behavior
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“The endogenous opioid system influences positive and negative motivational and affective states (Steiner & Gerfen 1998) and participates in the behavioral effects of several addictive drugs, including nicotine (Berrendero et al. 2005, Hadjiconstantinou & Neff 2010, Trigo et al. 2009).”
BackgroundWooltorton, J. R. A., Pidoplichko, V. I., Broide, R. S., & Dani, J. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03176.2003 · Cited by 363 · cited 3×
“The dense striatal acetylcholine esterase rapidly hydrolyzes the released ACh, preventing the appearance of long-lasting ACh signals that would strongly desensitize the high-affinity subtypes of nAChRs (Dani et al. 2000, Grady et al. 1994, Wooltorton et al. 2003).”
BackgroundSelf-citationFrequency-dependent modulation of dopamine release by nicotine
Zhang, H., & Sulzer, D. (2004) · Nature Neuroscience · doi:10.1038/nn1243 · Cited by 361
Chronic Exposure to Nicotine Upregulates the Human α4β2 Nicotinic Acetylcholine Receptor Function
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“One of the most direct and important neuroadaptations induced by chronic nicotine use is the subtype-specific upregulation of nAChRs (Buisson & Bertrand 2001; Changeux et al. 1984; Dani & Heinemann 1996; Flores et al. 1997; Mansvelder et al. 2002; Marks et al. 1983, 1992; Perry et al. 1999; Rezvani…”
BackgroundThe laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons
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“This influence of the PPT/LDT arises, at least in part, because these areas contribute to the phasic burst firing of DA neurons (Floresco et al. 2003, Lodge & Grace 2006).”
BackgroundReal-time chemical responses in the nucleus accumbens differentiate rewarding and aversive stimuli
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“In the NAc of rats, intraoral sucrose (i.e., rewarding) infusion increased DA levels, whereas quinine (i.e., aversive) infusion decreased DA levels (Roitman et al. 2008).”
BackgroundRodent model of nicotine abstinence syndrome
Malin, D. H., Lake, J. R., Newlin-Maultsby, P., Roberts, L. K., Lanier, J. G., Carter, V. A., Cunningham, J. S., & Wilson, O. B. (1992) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(92)90408-8 · Cited by 334 · cited 1×
“In rats, somatic signs of physical dependency include teethchattering, chewing, gasps, palpebral ptosis, tremors, shakes, and yawns (Malin et al. 1992).”
BackgroundDissociation of dopamine release in the nucleus accumbens from intracranial self-stimulation
Garris, P. A., Kilpatrick, M., Bunin, M. A., Michael, D., Walker, Q. D., & Wightman, R. M. (1999) · Nature · doi:10.1038/18019 · Cited by 327 · cited 1×
“Self-stimulation of the medial forebrain bundle facilitates DA release (Garris et al. 1999, Gratton et al. 1988, Phillips et al. 1989), and DA Annu Rev Neurosci.”
BackgroundAlkondon, M., Pereira, E. F. R., Barbosa, C. T. F., & Albuquerque, E. X. (1997) · PubMed · Cited by 326
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“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript receptor antagonists or DA neuron lesions inhibit brain self-stimulation (Fouriezos & Wise 1976, Lippa et al. 1973, Stellar & Corbett 1989).”
BackgroundSpontaneous Activity of Neostriatal Cholinergic InterneuronsIn Vitro
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“The ongoing activity of striatal cholinergic interneurons (Bennett & Wilson 1999) excites presynaptic nAChRs on the DA terminals (Jones et al. 2001), producing an increase of intraterminal calcium that enhances DA release (Grady et al. 1997, Wonnacott et al. 2000).”
BackgroundWeiss, F., Markou, A., Lorang, M. T., & Koob, G. F. (1992) · Brain Research · doi:10.1016/0006-8993(92)91327-b · Cited by 318
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“Interestingly, local re-expression of α7 in the VTA did not reinstate self-administration in α7 −/− mice (Pons et al. 2008), consistent with the pharmacological evidence indicating that the α7 subunit does not influence chronic nicotine self-administration in trained rats (Grottick & Higgins 2000)…”
BackgroundInfluentialDopaminergic Innervation of the Amygdala Is Highly Responsive to Stress
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“…in the PFC occurs during stressful and aversive stimuli and is implicated in anxiety, the elevated PFC DA during nicotine withdrawal may contribute to the aversive manifestations (Bradberry et al. 1991, Broersen et al. 2000, Inglis & Moghaddam 1999, Kawasaki et al. 2001, Thierry et al. 1976).”
BackgroundNeurobiology of the nicotine withdrawal syndrome
Kenny, P. J., & Markou, A. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00651-7 · Cited by 310 · cited 1×
“In the conditioned place-aversion paradigm, the animal learns to avoid the compartment in which nicotine withdrawal is experienced (Jackson et al. 2009, Kenny & Markou 2001).”
BackgroundSalas, R., Sturm, R., Boulter, J., & De Biasi, M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4934-08.2009 · Cited by 310 · cited 4×
“Physical signs of dependency are also absent in α5 −/− mice in which nicotine withdrawal occurs either spontaneously or upon nicotine cessation or is precipitated by mecamylamine injection (Salas et al. 2009).”
BackgroundInfluentialBoth Positive Reinforcement and Conditioned Aversion from Amphetamine and from Apomorphine in Rats
Wise, R. A., Yokel, R. A., & de Wit, H. (1976) · Science · doi:10.1126/science.1257748 · Cited by 306 · cited 1×
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript Dani et al. 2009, Hutchison & Riley 2008, Kassel et al. 2007, Simpson & Riley 2005, Wise et al. 1976).”
BackgroundBoulter, J., O'Shea-Greenfield, A., Duvoisin, R. M., Connolly, J. G., Wada, E., Jensen, A., Gardner, P. D., Ballivet, M., Deneris, E. S., & McKinnon, D. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39588-2 · Cited by 302 · cited 1×
“Attenuation of nicotine-induced seizure is also present in mice heterozygous for the α3 subunit, which is found in the same gene cluster that contains α5 and β4 (Boulter et al. 1990, Salas et al. 2004a).”
BackgroundDual Cholinergic Control of Fast-Spiking Interneurons in the Neostriatum
Koós, T. Z., & Tepper, J. M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-02-00529.2002 · Cited by 302 · cited 1×
“The background firing rate of striatal cholinergic neurons is ~6 Hz, providing ongoing acetylcholine (ACh) release via direct synaptic transmission and volume transmission (Dani & Bertrand 2007, de Rover et al. 2002, Koos & Tepper 2002, Wilson 2004).”
BackgroundHierarchical Control of Dopamine Neuron-Firing Patterns by Nicotinic Receptors
Mameli-Engvall, M., Evrard, A., Pons, S., Maskos, U., Svensson, T. H., Changeux, J.-P., & Faure, P. (2006) · Neuron · doi:10.1016/j.neuron.2006.05.007 · Cited by 296 · cited 9×
“…DA neurons via those and other nAChR subtypes (Pidoplichko et al. 1997), and nicotine modifies the firing modes and firing frequency of DA neurons through excitatory and inhibitory inputs and synaptic plasticity (Mameli-Engvall et al. 2006; Schilstrom et al. 2000, 2003; Zhang et al. 2009b).”
BackgroundInfluentialDrugs and Reinforcement Mechanisms: A Critical Review of the Catecholamine Theory
Fibiger, H. C. (1978) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.18.040178.000345 · Cited by 293
Nicotinic excitation of rat ventral tegmental neurones in vitro studied by intracellular recording
Calabresi, P., Lacey, M. G., & North, R. A. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb16873.x · Cited by 285 · cited 1×
“Each of these neuronal subpopulations expresses nAChRs of differing subunit compositions and in differing cellular localizations (Calabresi et al. 1989, Klink et al. 2001, Wooltorton et al. 2003).”
BackgroundSeverity of withdrawal symptoms as a predictor of outcome of an attempt to quit smoking
West, R. J., Hajek, P., & Belcher, M. (1989) · Psychological Medicine · doi:10.1017/s0033291700005705 · Cited by 279
Synaptic Plasticity and Nicotine Addiction
Dani, J. A., Ji, D., & Zhou, F.-M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00379-8 · Cited by 274 · cited 2×
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript glutamate receptors (GluRs) at locations mediating drug-associated memory (Dani et al. 2001, Kauer & Malenka 2007, Tang & Dani 2009), including at DA neurons (Gao et al. 2010, Placzek et al. 2009, Saal et al. 2003).”
BackgroundSelf-citationExley, R. A., & Cragg, S. J. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707510 · Cited by 271 · cited 1×
“This ongoing ACh release and breakdown produce a background of cholinergic activity in the striatum that has a number of functions, including regulation of DA release (Exley & Cragg 2008, Zhang et al. 2009a, Zhang & Sulzer 2004).”
BackgroundPicciotto, M. R., & Corrigall, W. A. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03338.2002 · Cited by 265 · cited 1×
“The PPT/LDT contribute to events associated with drug taking (Picciotto & Corrigall 2002), as exemplified by lesions in the PPT reducing nicotine self-administration (Lanca et al. 2000).”
BackgroundNicotine: from molecular mechanisms to behaviour
Wonnacott, S., Sidhpura, N., & Balfour, D. J. (2005) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2004.12.002 · Cited by 263 · cited 1×
“Acting via distinct anatomical distributions and cellular locations of nAChR subtypes, nicotine produces neuroadaptations through its influence over intracellular pathways (Wonnacott et al. 2005).”
BackgroundNicotine upregulates its own receptors through enhanced intracellular maturation
Sallette, J., Pons, S., Devillers-Thiery, A., Soudant, M., Prado de Carvalho, L., Changeux, J.-P., & Corringer, P. J. (2005) · Neuron · doi:10.1016/j.neuron.2005.03.029 · Cited by 261 · cited 1×
“Other mechanisms that likely contribute to upregulation are decreased surface receptor turnover (Peng et al. 1997) and increased receptor assembly at the endoplasmic reticulum (Corringer et al. 2006; Darsow et al. 2005; Rezvani et al. 2007, 2010; Sallette et al. 2005).”
BackgroundLaterodorsal tegmental projections to identified cell populations in the rat ventral tegmental area
Omelchenko, N., & Sesack, S. R. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20417 · Cited by 257 · cited 2×
“Rather, the PPT/LDT neurons provide potent glutamatergic excitation to the DA neurons projecting to the NAc (Omelchenko & Sesack 2005).”
BackgroundNicotine addiction: the possible role of functional upregulation
Buisson, B., & Bertrand, D. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01979-9 · Cited by 254 · cited 1×
“Isomerization of surface nAChRs to high-affinity nicotinic sites has also been proposed (Buisson & Bertrand 2002, Vallejo et al. 2005).”
BackgroundBalfour, D. (2004) · Nicotine & Tobacco Research · doi:10.1080/14622200412331324965 · Cited by 251 · cited 1×
“Likewise, this DA system plays a critical role in the acquisition of behaviors that are inappropriately reinforced by psychostimulant drugs, including nicotine (Balfour 2004, Corrigall 1999, Dani et al. 2009, Dani & Heinemann 1996, Di Chiara 2000, Mansvelder & McGehee 2002).”
BackgroundThe endogenous opioid system: A common substrate in drug addiction
Trigo, J. M., Martín‐García, E., Berrendero, F., Robledo, P., & Maldonado, R. J. (2009) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.10.011 · Cited by 250
George, O., Ghozland, S., Azar, M. R., Cottone, P., Zorrilla, E. P., Parsons, L. H., O'Dell, L. E., Richardson, H. N., & Koob, G. F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707585104 · Cited by 245 · cited 1×
“During nicotine withdrawal, corticotropin-releasing factor receptor CRF1 influences anxiety and brain reward functions (Bruijnzeel et al. 2009, George et al. 2007).”
BackgroundGrottick, A. J., & Higgins, G. A. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00305-3 · Cited by 240 · cited 1×
“…−/− mice (Pons et al. 2008), consistent with the pharmacological evidence indicating that the α7 subunit does not influence chronic nicotine self-administration in trained rats (Grottick & Higgins 2000) nor nicotine-induced conditioned place preference (Stolerman et al. 2004, Walters et al. 2006).”
BackgroundWalaas, I., & Fonnum, F. (1980) · Neuroscience · doi:10.1016/0306-4522(80)90071-8 · Cited by 235
Presynaptic nicotinic receptors modulating dopamine release in the rat striatum
Wonnacott, S., Kaiser, S., Mogg, A., Soliakov, L., & Jones, I. W. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00005-4 · Cited by 232 · cited 1×
“The ongoing activity of striatal cholinergic interneurons (Bennett & Wilson 1999) excites presynaptic nAChRs on the DA terminals (Jones et al. 2001), producing an increase of intraterminal calcium that enhances DA release (Grady et al. 1997, Wonnacott et al. 2000).”
BackgroundSmolka, M. N., Bühler, M., Klein, S., Zimmermann, U., Mann, K., Heinz, A., & Braus, D. F. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0080-x · Cited by 230 · cited 1×
“…M anuscript Powerful cravings also accompany withdrawal, and they may be precipitated by drugreinforced memories, such as the sight of a cigarette and the place associated with smoking (Dalley & Everitt 2009, Dani & Montague 2007, Shiffman et al. 2002, Smolka et al. 2005, Volkow et al. 2002).”
BackgroundChergui, K., Suaud‐Chagny, M., & Gonon, F. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90465-0 · Cited by 229 · cited 1×
“The frequency dependence and nicotinic modulation of DA release differ in the dorsolateral striatum and NAc shell (Chergui et al. 1994; Cragg 2003; Cragg et al. 2002; Zhang et al. 2009a,b).”
BackgroundSalas, R., Pieri, F., & De Biasi, M. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1939-04.2004 · Cited by 226 · cited 5×
“Attenuation of nicotine-induced seizure is also present in mice heterozygous for the α3 subunit, which is found in the same gene cluster that contains α5 and β4 (Boulter et al. 1990, Salas et al. 2004a).”
BackgroundResultInfluentialSelf-citationCryan, J. F., Bruijnzeel, A. W., Skjei, K. L., & Markou, A. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1445-7 · Cited by 223 · cited 1×
“Buproprion may aid smoking cessation, in part, by normalizing NAc DA levels, and those DA levels may in turn attenuate anhedonia and somatic withdrawal signs (Cryan et al. 2003, Paterson & Markou 2007).”
BackgroundCharacterization of spontaneous and precipitated nicotine withdrawal in the mouse
Damaj, M. I., Kao, W., & Martin, B. R. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.054908 · Cited by 222 · cited 3×
“Mecamylamine, which has a slightly higher affinity for α3β4* nAChRs than for β2* receptors, is the best antagonist at precipitating nicotine withdrawal (Damaj et al. 2003).”
BackgroundGrady, S. R., Moretti, M., Zoli, M., Marks, M. J., Zanardi, A., Pucci, L., Clementi, F., & Gotti, C. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5121-08.2009 · Cited by 222 · cited 1×
“In the mouse, the α5, α2, and β4 nAChR subunits are expressed at high levels in either MHb and/or IPN (De Biasi & Salas 2008, Grady et al. 2009), and no mRNA encoding for nAChR subunits can be detected in the LHb by in situ hybridization techniques.”
BackgroundThe mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice
Paterson, N. E., Semenova, S., Gasparini, F., & Markou, A. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1432-z · Cited by 220 · cited 1×
“…SENSORY SIGNALING IN THE MESOCORTICOLIMBIC SYSTEM Nicotine in both humans and animals follows an inverted U-shaped dose-response curve, with aversive effects coming into play at higher nicotine concentrations (Ashton et al. 1980, Fattore et al. 2002, Herskovic et al. 1986, Paterson et al. 2003).”
BackgroundPrinciples of addiction medicine
Ries, R. R., Fiellin, D. A., Miller, S. C., & Saitz, R. (2009) · Cited by 218
Watkins, S. S., Stinus, L., Koob, G. F., & Markou, A. (2000) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35389-3 · Cited by 214
Angulo, J. A., & McEwen, B. S. (1994) · Brain Research Reviews · doi:10.1016/0165-0173(94)90002-7 · Cited by 213 · cited 1×
“In addition, DA controls the synthesis of striatal dynorphin and enkephalin by affecting mRNA levels (Angulo & McEwen 1994, Hadjiconstantinou & Neff 2010).”
BackgroundWalters, C. L., Brown, S., Changeux, J.-P., Martin, B., & Damaj, M. I. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0295-x · Cited by 206 · cited 1×
“…−/− mice (Pons et al. 2008), consistent with the pharmacological evidence indicating that the α7 subunit does not influence chronic nicotine self-administration in trained rats (Grottick & Higgins 2000) nor nicotine-induced conditioned place preference (Stolerman et al. 2004, Walters et al. 2006).”
BackgroundFenster, C. P., Whitworth, T. L., Sheffield, E. B., Quick, M. W., & Lester, R. A. J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-12-04804.1999 · Cited by 204 · cited 1×
“The homeostatic response to desensitized (turned-off) receptors is upregulation (Dani & Heinemann 1996, Fenster et al. 1999, Picciotto et al. 2008).”
BackgroundGroenewegen, H. J., Ahlenius, S., Haber, S. N., Kowall, N. W., & Nauta, W. J. H. (1986) · The Journal of Comparative Neurology · doi:10.1002/cne.902490107 · Cited by 202 · cited 22×
“Although investigators originally postulated that the DA released from the VTA mediates only the hedonic or pleasurable effects of natural reinforcers and drugs in the NAc, evidence indicates that DA can signal events of opposite hedonic valence based on novelty or salience.”
BackgroundInfluentialChronic Nicotine Exposure Upregulates Nicotinic Receptors by a Novel Mechanism
Vallejo, Y. F. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.5240-04.2005 · Cited by 201
Hildebrand, B. E., Nomikos, G. G., Hertel, P., Schilström, B., & Svensson, T. H. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01135-9 · Cited by 200 · cited 1×
“Spontaneous or mecamylamine-precipitated nicotine withdrawal is associated with a decrease in extracellular DA levels in the NAc (Carboni et al. 2000, Gaddnas et al. 2002, Hildebrand et al. 1998, Rada et al. 2001, Rahman et al. 2004).”
BackgroundThe Nicotinic Acetylcholine Receptor Subunit α5 Mediates Short-Term Effects of Nicotine in Vivo
Salas, R., Orr‐Urtreger, A., Broide, R. S., Beaudet, A. L., Paylor, R. E., & Biasi, M. D. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.5.1059 · Cited by 200 · cited 2×
“Salas et al. (2003a, 2004a) observed that mice null for the α5 and β4 nAChR subunits are less sensitive to the acute effects of nicotine measured as hypolocomotion in the open field arena and nicotine-induced seizure activity.”
BackgroundSelf-citationPidoplichko, V. I., Noguchi, J., Areola, O. O., Liang, Y., Peterson, J., Zhang, T., & Dani, J. A. (2004) · Learning & Memory · doi:10.1101/lm.70004 · Cited by 196 · cited 4×
“The PPT/LDT cholinergic afferents boost glutamate afferent transmission via presynaptic nAChRs (Pidoplichko et al. 2004, Schilstrom et al. 2000) and provide some excitatory drive to GABA projection neurons and interneurons, mainly via β2containing (β2*) nAChRs (Mansvelder et al. 2002, Pidoplichko…”
BackgroundInfluentialSelf-citationThe neurobiology of tobacco addiction
Stolerman, I. P., & Shoaib, M. C. (1991) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(91)90638-9 · Cited by 195 · cited 2×
“…mechanistic actions underlie nicotine’s ability to enhance reward from brain stimulation, reinforce conditioned place preference, and support self-administration (Corrigall 1999, Dani et al. 2009, Dani & Harris 2005, Mameli-Engvall et al. 2006, Picciotto et al. 1998, Stolerman & Shoaib 1991).”
BackgroundPeng, X.-D., Gerzanich, V., Anand, R., Wang, F., & Lindstrom, J. M. (1997) · Molecular Pharmacology · doi:10.1124/mol.51.5.776 · Cited by 191 · cited 1×
“Other mechanisms that likely contribute to upregulation are decreased surface receptor turnover (Peng et al. 1997) and increased receptor assembly at the endoplasmic reticulum (Corringer et al. 2006; Darsow et al. 2005; Rezvani et al. 2007, 2010; Sallette et al. 2005).”
BackgroundPerrotti, L. I., Bolaños, C. A., Choi, K., Russo, S. J., Edwards, S., Ulery, P. G., Wallace, D. L., Self, D. W., Nestler, E. J., & Barrot, M. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04110.x · Cited by 178 · cited 22×
“Although investigators originally postulated that the DA released from the VTA mediates only the hedonic or pleasurable effects of natural reinforcers and drugs in the NAc, evidence indicates that DA can signal events of opposite hedonic valence based on novelty or salience.”
BackgroundInfluentialLaviolette, S. (2007) · Schizophrenia bulletin · doi:10.1093/schbul/sbm048 · Cited by 177 · cited 1×
“…involved in reinforcement (ventral striatum), learning and declarative memory (hippocampus), emotional memory (amygdala), and habit formation (dorsal striatum), as well as executive functions and working memory (PFC and orbitofrontal cortex) (Schultz W. 2007b, Laviolette 2007, Seamans & Yang 2004).”
BackgroundBasal forebrain in the context of schizophrenia
Heimer, L. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00039-9 · Cited by 176 · cited 1×
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript hippocampus, and the amygdala (Haber et al. 2000, Heimer 2000, Pennartz et al. 1994).”
BackgroundDopamine Signaling Differences in the Nucleus Accumbens and Dorsal Striatum Exploited by Nicotine
Zhang, T., Zhang, L., Liang, Y., Siapas, A. G., Zhou, F.-M., & Dani, J. A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0261-09.2009 · Cited by 170 · cited 20×
“…DA neurons via those and other nAChR subtypes (Pidoplichko et al. 1997), and nicotine modifies the firing modes and firing frequency of DA neurons through excitatory and inhibitory inputs and synaptic plasticity (Mameli-Engvall et al. 2006; Schilstrom et al. 2000, 2003; Zhang et al. 2009b).”
BackgroundMethodResultInfluentialSelf-citationJones, I. W., Bolam, J. P., & Wonnacott, S. (2001) · The Journal of Comparative Neurology · doi:10.1002/cne.1345 · Cited by 168 · cited 1×
“The ongoing activity of striatal cholinergic interneurons (Bennett & Wilson 1999) excites presynaptic nAChRs on the DA terminals (Jones et al. 2001), producing an increase of intraterminal calcium that enhances DA release (Grady et al. 1997, Wonnacott et al. 2000).”
BackgroundHarrison, A. A. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00237-2 · Cited by 167 · cited 1×
“Both spontaneous (Epping-Jordan et al. 1998, Harrison et al. 2001) and mecamylamine-precipitated (Watkins et al. 2000) nicotine withdrawal induce increases in self-stimulation thresholds.”
BackgroundNishikawa, T., Fage, D., & Scatton, B. (1986) · Brain Research · doi:10.1016/0006-8993(86)90347-1 · Cited by 166 · cited 1×
“In contrast, habenular lesions increase DA turnover in the NAc and PFC, reflecting an activation of the dopaminergic system (Lisoprawski et al. 1980, Nishikawa et al. 1986).”
BackgroundLester, H. A., Xiao, C., Srinivasan, R., Son, C. D., Miwa, J., Pantoja, R., Banghart, M. R., Dougherty, D. A., Goate, A. M., & Wang, J. C. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9090-7 · Cited by 163 · cited 1×
“Therefore, nicotine can influence intracellular processes indirectly via nAChRs and directly by entering the cytoplasm (Lester et al. 2009, Rezvani et al. 2007).”
BackgroundControls of tonic and phasic dopamine transmission in the dorsal and ventral striatum
Zhang, L., Doyon, W. M., Clark, J. J., Phillips, P. E. M., & Dani, J. A. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.056317 · Cited by 161
Routtenberg, A., & Lindy, J. (1965) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0022365 · Cited by 160 · cited 1×
“…of the brain reward circuitry was spearheaded in the 1950s by Olds and Milner (Olds 1958, Olds & Milner 1954), who showed that rats work incessantly to self-administer intracranial electrical stimulation to certain regions of the brain (Conover et al. 1994, Routtenberg & Lindy 1965, Spies 1965).”
BackgroundKim, U., & Chang, S.-Y. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20410 · Cited by 159
Lecca, S., Melis, M., Luchicchi, A., Ennas, M. G., Castelli, M. P., Muntoni, A. L., & Pistis, M. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.190 · Cited by 158 · cited 1×
“Nicotine increases the RMTg neuron activity (Lecca et al. 2010).”
Nicotine self-administration in animals as a dependence model
Corrigall, W. A. (1999) · Nicotine & Tobacco Research · doi:10.1080/14622299050011121 · Cited by 156 · cited 2×
“Likewise, this DA system plays a critical role in the acquisition of behaviors that are inappropriately reinforced by psychostimulant drugs, including nicotine (Balfour 2004, Corrigall 1999, Dani et al. 2009, Dani & Heinemann 1996, Di Chiara 2000, Mansvelder & McGehee 2002).”
BackgroundHabenular and interpeduncularis nuclei: shared components in multiple-function networks.
Klemm, W. R. (2004) · PubMed · Cited by 153
Salminen, O., Drapeau, J. A., McIntosh, J. M., Collins, A. C., Marks, M. J., & Grady, S. R. (2007) · Molecular Pharmacology · doi:10.1124/mol.106.031492 · Cited by 151 · cited 1×
“Thus, β2* nAChRs in combinations with both α4 and α6 subunits are important for the reinforcing properties of nicotine, and the α4 and α6 subunits cannot completely substitute for each other even though they are abundantly expressed in VTA neurons (Champtiaux et al. 2003, Salminen et al. 2007).”
BackgroundNew insights on the subcortical representation of reward
Hikosaka, O., Bromberg-Martin, E. S., Hong, S., & Matsumoto, M. (2008) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2008.07.002 · Cited by 149 · cited 2×
“For example, LHb neurons increase their firing in the absence of predicted reward and decrease their firing upon delivery of reward, which is opposite from the usual firing of DA neurons (Hikosaka et al. 2008, Matsumoto & Hikosaka 2007).”
BackgroundDual effects of nicotine on dopamine neurons mediated by different nicotinic receptor subtypes
Schilström, B., Rawal, N., Mameli-Engvall, M., Nomikos, G. G., & Svensson, T. H. (2003) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145702003188 · Cited by 149 · cited 2×
“…induces phasic bursts from VTA/SNc DA neurons (Figure 1b) that innervate much of the dorsal to ventral extent of the striatum (Grenhoff et al. 1986, Pidoplichko et al. 1997, Schilstrom et al. 2003, Zhang et al. 2009b), suggesting that the DA signal should be comparable throughout the striatum.”
BackgroundMuscarinic and Nicotinic Cholinergic Mechanisms in the Mesostriatal Dopamine Systems
Zhou, F.-M., Wilson, C. J., & Dani, J. A. (2003) · The Neuroscientist · doi:10.1177/1073858402239588 · Cited by 146 · cited 1×
“…are expressed on DA neuron fibers and terminals, and the activity of those nAChRs, particularly containing the β2, α4, and α6 subunits (Pons et al. 2008), is highly regulated by ongoing striatal cholinergic interneuron discharges and dense acetylcholine esterase activity (Zhou et al. 2001, 2003).”
BackgroundSelf-citationWithdrawal from Chronic Nicotine Administration Impairs Contextual Fear Conditioning in C57BL/6 Mice
Davis, J. A., James, J. R., Siegel, S. J., & Gould, T. J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2853-05.2005 · Cited by 146 · cited 1×
“The conditioned fear paradigm can be used to measure the cognitive symptoms of withdrawal (Davis et al. 2005) as nicotine withdrawal produces deficits in contextual fear conditioning and affects the acquisition of learned responses (Portugal et al. 2008).”
Winter, C., Vollmayr, B., Djodari-Irani, A., Klein, J., & Sartorius, A. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.07.034 · Cited by 145
Berrendero, F., Mendizábal, V. E., Robledo, P., Galeote, L., Bilkei‐Gorzó, A., Zimmer, A., & Maldonado, R. J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3008-04.2005 · Cited by 142 · cited 1×
“The endogenous opioid system influences positive and negative motivational and affective states (Steiner & Gerfen 1998) and participates in the behavioral effects of several addictive drugs, including nicotine (Berrendero et al. 2005, Hadjiconstantinou & Neff 2010, Trigo et al. 2009).”
BackgroundFlores, C. M., Dávila‐García, M. I., Ulrich‐Lai, Y. M., & Kellar, K. J. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69052216.x · Cited by 142 · cited 1×
“…by chronic nicotine use is the subtype-specific upregulation of nAChRs (Buisson & Bertrand 2001; Changeux et al. 1984; Dani & Heinemann 1996; Flores et al. 1997; Mansvelder et al. 2002; Marks et al. 1983, 1992; Perry et al. 1999; Rezvani et al. 2007, 2009; Rowell & Wonnacott 1990; Schwartz…”
BackgroundRada, P., Jensen, K., & Hoebel, B. (2001) · Psychopharmacology · doi:10.1007/s002130100781 · Cited by 141 · cited 1×
“Spontaneous or mecamylamine-precipitated nicotine withdrawal is associated with a decrease in extracellular DA levels in the NAc (Carboni et al. 2000, Gaddnas et al. 2002, Hildebrand et al. 1998, Rada et al. 2001, Rahman et al. 2004).”
BackgroundShepard, D. S., Holcomb, H. H., & Gold, J. M. (2005) · Schizophrenia Bulletin · doi:10.1093/schbul/sbj083 · Cited by 140
Berrendero, F., Robledo, P., Trigo, J. M., Martín-García, E., & Maldonado, R. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.02.006 · Cited by 140 · cited 1×
“Chronic nicotine exposure also has indirect effects on motivational systems by altering synthesis and release of opioid peptides in a time-dependent and peptide-specific fashion (Berrendero et al. 2010).”
BackgroundMaze exploration and learning in C. elegans
Qin, J., & Wheeler, A. R. (2006) · Lab on a Chip · doi:10.1039/b613414a · Cited by 139 · cited 1×
“Therefore, reward mechanisms are observed across species, from insects to primates (Hodos 1961, Lau et al. 2006, McClure et al. 2007, Qin & Wheeler 2007, Wise 2006).”
BackgroundMaskos, U. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.5 · Cited by 139 · cited 1×
“In addition, the PPT/LDT cholinergic afferents have important endogenous influences over DA neurons by acting via nAChRs (Maskos 2008, 2010).”
BackgroundCragg, S. J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-10-04378.2003 · Cited by 138 · cited 5×
“As a consequence, low-frequency, tonic DA release is inhibited (Rice & Cragg 2004, Zhang & Sulzer 2004, Zhou et al. 2001), but phasic DA release is regulated differently, such that phasic bursts induce large DA signals (Cragg 2003; Rice & Cragg 2004; Zhang et al. 2009a,b).”
BackgroundMethodInfluentialExcitability of Dopamine Neurons: Modulation and Physiological Consequences
White, F., Hu, X., Marinelli, M., & Rudick, C. N. (2006) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152706784111542 · Cited by 136
Bruijnzeel, A. W., Prado, M., & Isaac, S. K. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.01.010 · Cited by 132 · cited 1×
“During nicotine withdrawal, corticotropin-releasing factor receptor CRF1 influences anxiety and brain reward functions (Bruijnzeel et al. 2009, George et al. 2007).”
BackgroundBOLD responses to negative reward prediction errors in human habenula
Salas (2010) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2010.00036 · Cited by 131
Lisoprawski, A., Herve, D., Blanc, G., Glowinski, J., & Tassin, J. P. (1980) · Brain Research · doi:10.1016/0006-8993(80)90135-3 · Cited by 130 · cited 1×
“In contrast, habenular lesions increase DA turnover in the NAc and PFC, reflecting an activation of the dopaminergic system (Lisoprawski et al. 1980, Nishikawa et al. 1986).”
BackgroundBruijnzeel, A. W., & Gold, M. S. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.01.007 · Cited by 129 · cited 1×
“The negative emotional state produced by the combination of withdrawal symptoms causes enough distress to become a deterrent to abstinence and a drive to relapse (Bruijnzeel & Gold 2005, Koob & Le Moal 2005, West et al. 1989).”
BackgroundAltered Anxiety-Related Responses in Mutant Mice Lacking the β4 Subunit of the Nicotinic Receptor
Salas, R., Pieri, F., Fung, B., Dani, J. A., & De Biasi, M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06255.2003 · Cited by 128 · cited 2×
“Salas et al. (2003a, 2004a) observed that mice null for the α5 and β4 nAChR subunits are less sensitive to the acute effects of nicotine measured as hypolocomotion in the open field arena and nicotine-induced seizure activity.”
BackgroundSelf-citationNeurochemical mediation of reward: A significant role for dopamine?
LIPPA, A. S., Antelman, S. M., Fisher, A. E., & Canfield, D. R. (1973) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(73)90050-6 · Cited by 127 · cited 1×
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript receptor antagonists or DA neuron lesions inhibit brain self-stimulation (Fouriezos & Wise 1976, Lippa et al. 1973, Stellar & Corbett 1989).”
BackgroundDrenan, R. M., Grady, S. R., Steele, A. D., McKinney, S., Patzlaff, N. E., McIntosh, J. M., Marks, M. J., Miwa, J. M., & Lester, H. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2056-10.2010 · Cited by 127 · cited 1×
“In the midbrain, nAChRs comprising the β2 nAChR subunit in combination with α4 and/or α6 subunits are essential for nicotine-induced reinforcement and the DA signal (Drenan et al. 2010, Mameli-Engvall et al. 2006, Picciotto et al. 1998, Pons et al. 2008, Tapper et al. 2004).”
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“In particular, dynorphins decrease and enkephalins increase the release of DA (Devine et al. 1993; Di Chiara & Imperato 1988; Longoni et al. 1991; Pentney & Gratton 1991; Spanagel et al. 1990a,b, 1992).”
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Cited by
Sorted by citations
Cholinergic modulation of the hippocampal region and memory function
Haam, J., & Yakel, J. L. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14052 · Cited by 468
Neuronal nicotinic acetylcholine receptor structure and function and response to nicotine
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“Finally, although the molecules highlighted here are clearly involved in DA mesolimbic transmission and reward responses, this represents only a brief overview and readers are encouraged to see other recent reviews of this topic [86,91-93].”
BackgroundEmerging Molecular Mechanisms of Signal Transduction in Pentameric Ligand-Gated Ion Channels
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“…should be mentioned. nAChRs expressed in the ventral tegmental area have been found to be responsible for nicotine and tobacco addiction (De Biasi and Dani, 2011), and synthetic positive allosteric modulators (PAMs) targeting neuronal a7nAChRs were developed as potential neuro-protective…”
BackgroundReinstatement of nicotine seeking is mediated by glutamatergic plasticity
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Metadata
- Authors
- De Biasi, M., & Dani, J. A.
- Affiliations
- Baylor College of Medicine (US)
- ORCID
- Dani, John A.
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2011-07-21
- Volume
- 34
- Issue
- 1
- Pages
- 105-130
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC3137256
- OpenAlex
- W2165425515
- Semantic Scholar
- c6462f78d05c8073c59243cb5544623aa43f3c33
- Cited by
- 366
- References
- 305
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 20 · 2023: 13 · 2022: 13 · 2021: 14 · 2020: 32 · 2019: 23 · 2018: 22 · 2017: 36 · 2016: 28 · 2015: 29 · 2014: 42 · 2013: 27 · 2012: 33
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research Institute
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- National Institute on Drug Abuse (R21DA029157, DA09411, DA017173, R01DA017173, R01DA009411, DA029157)
- National Cancer Institute (U19CA148127)
- National Institute of Neurological Disorders and Stroke (NS 21229, R37NS021229, R01NS021229)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, nicotine dependence, nicotine withdrawal, reward, mesocorticolimbic dopamine system, nicotinic acetylcholine receptors, nicotinic receptor subunits, dopaminergic neurons, neural adaptation, habenula, tobacco use
- MeSH terms
- Animals, Cerebral Cortex, Dopamine, Humans, Limbic System, Neuronal Plasticity, Neurons, Nicotine, Receptors, Nicotinic, Reward, Substance Withdrawal Syndrome, Behavior, Addictive
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
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