Mechanisms of Nicotine Addiction

The α6 subunit appears to be selectively expressed in DA neurons.

“The α6 subunit appears to be selectively expressed in DA neurons (Le Novere et al. 1996;Drenan et al. 2008b)”

• cites Le Novere et al. 1996 sourcePartly supported

  The title in our indexed copy says α6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain. The available passages do not specifically identify DA neurons or establish selective expression in them; they support the broader localization claim only. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites Drenan et al. 2008bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Knockout of the α4 subunit abolishes intracerebroventricular self-administration of nicotine.

“Similarly, knockout of the α4 subunit abolishes intracerebroventricular (i.c.v.) selfadministration of nicotine, consistent with evidence that α4/β2 Ã nAChRs are required for depolarization of DA neurons in the VTA (Exley et al. 2011;McGranahan et al. 2011).”

• cites Exley et al. 2011 sourcePartly supported

  The Results report that α4-knockout mice did not sustain nicotine self-administration beyond session 3, supporting the loss of sustained self-administration. But the experiment delivered nicotine intracranially into the VTA, not intracerebroventricularly, and the mice showed initial approach behavior rather than an immediate abolition of the response. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites McGranahan et al. 2011 sourcePartly supported

  The Results section, “α4*-nAChRs on Dopaminergic Neurons Mediate Nicotine Reward” (page unavailable), reports that α4-knockout mice did not develop nicotine conditioned place preference. The Methods section, “Conditioned Place Preference” (page unavailable), describes intraperitoneal nicotine injections, not intracerebroventricular self-administration. The paper supports a loss of nicotine reward in this test, but not the specified self-administration claim. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Nicotine can desensitize β2* nAChRs on GABAergic inputs to DA neurons, shifting from mixed excitation and inhibition to more unmixed stimulation of nAChRs on presynaptic glutamatergic terminals.

“In addition, nicotine can desensitize β2 Ã nAChRs on GABAergic inputs to DA neurons, resulting in a shift from mixed excitation and inhibition of DA neurons by nicotine, to a more unmixed stimulation of nAChRs on presynaptic glutamatergic terminals (Mansvelder et al. 2002;Wooltorton et al. 2003).”

• cites Mansvelder et al. 2002 sourceNot checked — no full text of the source
• cites Wooltorton et al. 2003 sourceSupported

The MHb projects almost exclusively to the IPN via the fasciculus retroflexus.

“Unlike LHb, the MHb projects almost exclusively to the interpeduncular nucleus (IPN) via the fasciculus retroflexus (Fr) (Lecourtier and Kelly 2007;Hikosaka 2010).”

• cites Lecourtier and Kelly 2007 sourceNot checked — no full text of the source
• cites Hikosaka 2010 sourcePartly supported

  The Abstract (page unavailable) says that MHb neurons project to the IPN and identifies the fasciculus retroflexus as the habenula’s output tract. It contrasts this with LHb projections to other midbrain areas, but does not establish that MHb projections to the IPN are almost exclusive. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Mice lacking the α6 subunit do not acquire nicotine self-administration.

“Mice lacking the α6 subunit do not acquire nicotine self-administration (Pons et al. 2008).”

• cites Pons et al. 2008 sourceSupported

Chemical inactivation of the MHb or IPN with lidocaine, or disruption of NMDA receptor-mediated glutamatergic transmission with LY2358959, increased nicotine self-administration in rats similarly to α5 knockout.

“Chemical inactivation of the MHb or the IPN using the local anesthetic lidocaine, or disruption of N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic transmission in these sites using the competitive antagonist LY2358959, increased nicotine self-administration behavior in rats in a manner similar to the α5 nAChR subunit knockout mice (Fowler et al. 2011).”

• cites Fowler et al. 2011 sourcePartly supported

  In “Habenular-IPN activity limits nicotine intake,” lidocaine inactivation of the IPN or MHb and NMDA-receptor antagonism at those sites increased nicotine self-administration in rats, consistent with the knockout findings reported elsewhere in the paper. The source names the antagonist LY235959, not LY2358959; it also reports the MHb effects only at a higher nicotine dose. Page numbers were not provided in the supplied passages. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

α5 knockout mice consumed more nicotine only when higher unit doses were available.

“Interestingly, the knockout mice consumed more nicotine only when higher unit doses of the drug were available (Fowler et al. 2011).”

• cites Fowler et al. 2011 sourcePartly supported

  In “α5* nAChRs control nicotine intake” (page unavailable), the paper reports that knockout mice consumed greater amounts as the unit dose increased and responded more vigorously especially at higher doses. It does not establish the claim’s stricter “only” condition: the passage says “especially,” not that increased consumption occurred exclusively at higher doses. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Mice with a null mutation in the α5 subunit intravenously self-administered far more nicotine than wild-type littermates.

“Consistent with an important role for α5 Ã nAChRs in regulating nicotine intake, it was recently shown that mice with null mutation in this subunit intravenously self-administered far more nicotine than their wild-type littermates (Fowler et al. 2011).”

• cites Fowler et al. 2011 sourceSupported

RNA interference-mediated knockdown of α5 nAChR subunits in the MHb-IPN pathway in rats increased nicotine intake at higher unit doses, similar to α5 knockout mice.

“Conversely, RNA interference-mediated knockdown of α5 nAChR subunits in the MHb-IPN pathway in rats resulted in increased nicotine intake at higher unit doses of the drug, very similar to the same behavioral profile detected in the knockout mice (Fowler et al. 2011).”

• cites Fowler et al. 2011 sourceSupported

Chronic nicotine exposure increases action potential firing and nicotine sensitivity of MHb and IPN neurons.

“Interestingly, chronic nicotine exposure increases action potential firing and nicotine sensitivity of MHb and IPN neurons (Arvin et al. 2019).”

• cites Arvin et al. 2019 sourcePartly supported

  The Discussion (page not provided) reports enhanced action-potential firing in MHb neurons and increased nicotinic receptor function in MHb and IPN neurons. The section on nicotine sensitivity in rostral IPN neurons reports stronger nicotine-evoked depolarization, but does not report increased action-potential firing in IPN neurons; most recorded IPN neurons were not spontaneously firing. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Knockdown of α5 nAChR subunits in the MHb-IPN pathway in rats decreased sensitivity to the aversive actions of higher nicotine doses compared with controls, as measured by ICSS reward thresholds.

“Finally, knockdown of α5 nAChR subunits in the MHb-IPN pathway in rats decreased their sensitivity to the reward-inhibiting (i.e., aversive) actions of higher nicotine doses compared with control rats, as measured by nicotine-induced elevations of intracranial self-stimulation (ICSS) reward thresholds (Fowler et al. 2011).”

• cites Fowler et al. 2011 sourceSupported

The MHb-IPN pathway of α5 knockout mice was far less sensitive to nicotine-induced activation than that of wild-type mice, as measured by Fos immunoreactivity.

“By using Fos immunoreactivity as a measure of neuronal activation, it was shown that the MHb-IPN pathway of the knockout mice was far less sensitive to nicotine-induced activation than wild-type mice (Fowler et al. 2011).”

• cites Fowler et al. 2011 sourceSupported

Virus-mediated reexpression of the α5 nAChR subunit in the MHb-IPN pathway of knockout mice abolished the increased nicotine intake seen at higher doses.

“Virus-mediated reexpression of the α5 nAChR subunit in the MHb-IPN pathway of knockout mice abolished the increased nicotine intake seen at higher doses of nicotine (Fowler et al. 2011).”

• cites Fowler et al. 2011 sourceSupported

Allelic variation in the α5/α3/β4 nAChR subunit gene cluster at chromosome 15q25 significantly increases risk of tobacco addiction.

“It has been shown that allelic variation in the α5/α3/β4 nAChR subunit gene cluster located in chromosome region 15q25 significantly increases risk of tobacco addiction (Saccone et al. 2007;Berrettini et al. 2008;Lips et al. 2010).”

• cites Saccone et al. 2007 sourceSupported
• cites Berrettini et al. 2008 sourceSupported
• cites Lips et al. 2010 sourcePartly supported

  The Results and Discussion report that a variant in the 15q25 receptor-gene cluster is associated with smoking more cigarettes per day and with heavy smoking. They do not establish the claimed significant increase in risk of tobacco addiction: the paper distinguishes smoking quantity from nicotine dependence, and the Results find no association with smoking initiation or cessation. Page numbers are not available in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

GLP-1-immunoreactive fibers can be detected in the IPN of mice.

“Consistent with this possibility, GLP-1-immunoreactive fibers can be detected in the IPN of mice (Tuesta et al. 2017).”

• cites Tuesta et al. 2017 sourceSupported

RNA interference-mediated knockdown of GLP-1 receptor transcripts in MHb neurons increased nicotine intake in rats, particularly when higher unit doses were available.

“Consistent with this hypothesis, RNA interference-mediated knockdown of GLP-1 receptor transcripts in MHb neurons increased nicotine intake in rats, particularly when higher unit doses were available (Tuesta et al. 2017).”

• cites Tuesta et al. 2017 sourceSupported

Infusion of the GLP-1 receptor antagonist exendin-(9-39)-amide into the IPN increased nicotine intake in rats.

“Infusion of the GLP-1 receptor antagonist exendin-(9-39)-amide (Ex-9) into the IPN similarly increased nicotine intake in rats (Tuesta et al. 2017).”

• cites Tuesta et al. 2017 sourceSupported

Nicotine self-administration behavior is markedly enhanced by TCF7L2 deficiency in Tcf7l2 mutant rats.

“Using a line of Tcf7l2 mutant (Tcf7l2 mut ) rats in which the DNA-binding do-main of TCF7L2 was deleted using zinc finger nucleases it was shown that nicotine self-administration behavior is markedly enhanced by TCF7L2 deficiency (Duncan et al. 2019).”

• cites Duncan et al. 2019 sourcePartly supported

  The “Habenular Tcf7l2 regulates nicotine intake” section reports that Tcf7l2 mutant rats responded far more vigorously than wild-type rats for intravenous nicotine, supporting the behavioral claim. However, the citing sentence says the DNA-binding domain was deleted; the source says zinc finger nucleases deleted the β-catenin-binding domain. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

TCF7L2 is highly enriched in MHb neurons.

“Notably, TCF7L2 is highly enriched in MHb neurons (Duncan et al. 2019).”

• cites Duncan et al. 2019 sourceSupported

When channelrhodopsin-2 is expressed in GLP-1 neurons in the NTS, optical stimulation of GLP-1 terminals increases the frequency but not the amplitude of oEPSCs in IPN neurons.

“Further-more, when channelrhodopsin-2 is expressed in GLP-1 neurons in the NTS, optical stimulation of GLP-1 terminals increased the frequency but not the amplitude of postsynaptic currents (oEPSCs) in IPN neurons (Tuesta et al. 2017).”

• cites Tuesta et al. 2017 sourcePartly supported

  The Results section (‘GLP-1 stimulates habenular inputs to the interpeduncular nucleus’) reports that stimulation of ChR2-expressing GLP-1 terminals increased EPSC frequency but not amplitude in IPN neurons. The claim omits a decisive condition: this occurred with high-frequency (20 Hz) stimulation, not low-frequency (1 Hz) stimulation. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

α2 subunits are highly enriched in the IPN, similar to α5 subunits.

“Similar to α5 subunits, α2 subunits are highly enriched in the IPN (Grady et al. 2009).”

• cites Grady et al. 2009 sourcePartly supported

  The Results (Subunit composition of nAChRs in rat interpeduncular nucleus; page unavailable) report α2 and α5 in the IPN, but classify both as present at moderate levels, not high levels. The Discussion (Native subtypes in the habenulo-interpeduncular system; page unavailable) says α2β2* receptors are restricted to the IPN relative to the habenula. That supports IPN localization, but not the claim that α2 and α5 are both highly enriched there. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The amplitude of nicotine-evoked nAChR currents in MHb slices was similar in wild-type and TCF7L2-deficient rats.

“Using whole-cell recordings to assess pharmacologically isolated nAChR currents in MHb slices, it was shown that the amplitude of nicotine-evoked nAChR currents were similar in wild-type and TCF7L2-deficent rats (Duncan et al. 2019).”

• cites Duncan et al. 2019 sourceSupported

nAChRs in the MHb of TCF7L2-deficient rats failed to recover from nicotine-induced desensitization, unlike nAChRs in wild-type rats.

“However, unlike nAChRs in the MHb of wild-type rats, nAChRs failed to recover from nicotine-induced desensitization in TCF7L2deficent rats (Duncan et al. 2019).”

• cites Duncan et al. 2019 sourceSupported

Chemogenetic activation of GLP-1 neurons in the NTS decreased nicotine intake in mice.

“Chemogenetic activation of GLP-1 neurons in the NTS similarly decreased nicotine intake in mice (Tuesta et al. 2017).”

• cites Tuesta et al. 2017 sourceSupported

Systemic delivery of the GLP-1 receptor agonist exendin-4 or the DPP-4 inhibitor sitagliptin decreased responding for nicotine infusions but not food rewards in mice.

“Systemic delivery of the GLP-1 receptor agonist exendin-4 (Ex4), or the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin (to inhibit GLP-1 breakdown) decreased responding for nicotine infusions but not food rewards in mice (Tuesta et al. 2017).”

• cites Tuesta et al. 2017 sourcePartly supported

  The Results section (“GLP-1 regulates nicotine intake”; page not available) reports that Ex-4 decreased nicotine intake in mice without altering food-reward responding, and that sitagliptin also decreased nicotine self-administration. It does not specifically report a food-reward test for sitagliptin, so the claim that neither drug affected food responding goes beyond the drug-specific results, despite the Discussion’s broader statement that food responding was unaffected by GLP-1 manipulations. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Inhibition of TCF7L2 activity in the MHb, by CRISPR-Cas9 cleavage in mice or siRNAs in rats, dramatically increases nicotine intake.

“Inhibition of TCF7L2 activity in the MHb, accomplished in mice by CRISPR-Cas9 cleavage of Tcf7l2 DNA or in rats by local delivery of short interfering RNAs to knock down Tcf7l2 transcripts, dramatically increases nicotine intake (Duncan et al. 2019).”

• cites Duncan et al. 2019 sourceSupported

Infusion of Ex-4 into the IPN decreased nicotine intake in rats.

“Conversely, infusion of Ex-4 into the IPN decreased nicotine intake in rats (Tuesta et al. 2017).”

• cites Tuesta et al. 2017 sourceSupported

Nicotinic partial agonists are effective in human smokers.

“and in human smokers (Philip et al. 2009)”

• cites Philip et al. 2009 sourcePartly supported

  The Introduction identifies varenicline as a nicotinic partial agonist, and the Abstract Results report improved depressive symptoms and reduced smoking among depressed smokers who received it. But this eight-week, open-label study of one drug does not establish that nicotinic partial agonists as a class are effective in human smokers generally; the Discussion says the findings suggest varenicline may have antidepressant properties in smokers with treatment-resistant depression. No page numbers are available in our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Infusion of mecamylamine into the BLA decreases stress-induced immobility.

“Infusion of the broad nAChR antagonist mecamylamine into the BLA decreases stress-induced immobility”

• cites Mineur et al. 2016 sourceSupported

Female but not male mice lacking the α5 nAChR subunit show reduced anxiety-like behavior.

“female, but not male, knockout mice lacking the α5 subunit showed reduced anxiety-like behavior”

• cites Gangitano et al. 2009 sourceSupported

Chronic nicotine administration increases anxiety-like behavior in female mice but not in male mice.

“chronic administration of nicotine increased anxiety-like behavior in female, but not male, mice (Caldarone et al. 2008)”

• cites Caldarone et al. 2008 sourceSupported

Elevated ACh levels observed in human subjects who are actively depressed contribute to the disorder.

“supports the idea that the elevated ACh levels observed in human subjects who are actively depressed contributes to the disorder (Saricicek et al. 2012;Hannestad et al. 2013).”

• cites Saricicek et al. 2012 sourcePartly supported

  The Discussion reports lower β2*-nAChR availability in actively depressed patients and suggests that increased extracellular ACh, rather than fewer receptors, likely explains it. ACh levels were inferred rather than directly observed, and this study does not establish that the inferred increase causes or contributes to depression. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Hannestad et al. 2013 sourcePartly supported

  The Results report lower receptor availability in actively depressed subjects, not a direct measurement of elevated ACh. The Discussion suggests that higher extracellular ACh may explain the finding and could be associated with depression, but it does not establish that elevated ACh was observed or that it contributes causally to the disorder. No page numbers are available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Mice lacking the β4 nAChR subunit show less anxiety-like behavior at baseline.

“knockout mice lacking the β4 subunit show less anxiety-like behaviors at baseline (Salas et al. 2003)”

• cites Salas et al. 2003 sourcePartly supported

  The Results report that β4-knockout mice behaved as though they were less anxious in the elevated-plus maze, and the Introduction also cites increased climbing in the staircase maze. But the effect was test-specific: behavior was unchanged in three other tests, and social isolation produced a stronger anxiety-related response. The unqualified claim of less anxiety-like behavior at baseline overgeneralizes those findings. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The reduced anxiety-like behavior in female α5 knockout mice may be related to progesterone effects on α5 subunit expression.

“and this may be related to progesterone effects on α5 subunit expression (Gangitano et al. 2009)”

• cites Gangitano et al. 2009 sourceSupported

The effects of the partial agonist sazetidine could be blocked with mecamylamine.

“the effects of the partial agonist sazetidine could be blocked with mecamylamine (Caldarone et al. 2011)”

• cites Caldarone et al. 2011 sourceSupported

Nicotinic partial agonists are effective in mouse models of antidepressant efficacy.

“nicotinic partial agonists, that would be expected to decrease activity of acetylcholine at endogenous nAChRs when cholinergic tone is high but increase activity of nAChRs when cholinergic tone is low, are effective in mouse models of antidepressant efficacy (Mineur et al. 2007(Mineur et al. , 2009b(Mineur et al. , 2011a;;Rollema et al. 2009;Caldarone et al. 2011)”

• cites Mineur et al. 2007 sourceSupported
• cites Rollema et al. 2009 sourceSupported
• cites Caldarone et al. 2011 sourceSupported

Modulation of nicotinic function through the lynx1 protein is important for regulating the critical period for activity-dependent visual system development.

“modulation of nicotinic function through the lynx1 protein is also important for regulating the critical period for activity-dependent visual system development (Morishita et al. 2010).”

• cites Morishita et al. 2010 sourceSupported

Both POMC and NPY neurons express almost all nAChR subunits.

“both POMC and NPY neurons express almost all nAChR subunits”

• cites Calarco et al. 2018 sourcePartly supported

  The Results section (page not available) detects mRNAs for six nAChR subunits in both POMC and AgRP cell populations, which supports expression of several subunits. It also says α2, α5 and β3 were not reliably detected in either population, so “almost all” overstates the finding. The study measures AgRP rather than NPY neurons specifically, and its Discussion cautions that not every AgRP or POMC cell expresses each subunit. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Nicotine administration during the early postnatal period alters performance in the passive avoidance task in normal mice and in mice with expression of β2 nAChRs exclusively in corticothalamic neurons.

“Nicotine administration during this same period alters performance in the passive avoidance task in normal mice as well as in mice with expression of β2 Ã nAChRs exclusively in corticothalamic neurons (Heath et al. 2010)”

• cites Heath et al. 2010 sourcePartly supported

  The Results section reports that nicotine exposure from birth to weaning altered passive avoidance in mice. It also reports altered performance in mice expressing β2-containing nAChRs exclusively in corticothalamic neurons, but those mice received nicotine throughout gestation as well as postnatally; the paper does not establish the effect of postnatal-only exposure in that group (page not available in our copy). (LLM, conf=0.87)

  Experimental — accuracy not yet measured

nAChRs on glutamatergic thalamocortical neurons impinging on layer 5 pyramidal neurons in the prefrontal cortex are an important site for nAChR control of attention.

“Studies in rodents have also implicated nAChRs on glutamatergic thalamocortical neurons impinging on layer 5 pyramidal neurons in the prefrontal cortex as an important site for nAChR control of attention (Lambe et al. 2005;Bailey et al. 2010).”

• cites Lambe et al. 2005 sourceSupported
• cites Bailey et al. 2010 sourcePartly supported

  The Introduction and Discussion support a role for prefrontal nAChRs in attention. But this paper identifies nAChRs on layer VI pyramidal neurons that project from cortex to thalamus; it does not establish the claimed site on thalamocortical neurons impinging on layer 5 pyramidal neurons. No page numbers were provided in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Rapid acetylcholine transients in the mPFC are correlated with attention to brief cues.

“rapid acetylcholine transients in the mPFC are correlated with attention to brief cues”

• cites Parikh et al. 2007 sourceNot checked — no full text of the source
• cites Parikh et al. 2008 sourceSupported

Mice lacking the β2, but not the α7, subunit show impaired performance in an attentional task.

“mice lacking the β2, but not the α7, subunit show impaired performance in an attentional task (Parikh et al. 2007(Parikh et al. , 2008)).”

• cites Parikh et al. 2007 sourceNot checked — no full text of the source
• cites Parikh et al. 2008 sourceCould not verify

  The Subjects section describes experiments in rats, not mice lacking receptor subunits. The Discussion mentions that an α7-selective antagonist did not impair attentional performance, but does not report the claimed comparison between β2- and α7-deficient mice. Searches for knockout mice and the two subunits found no passage establishing that comparison; page numbers were unavailable in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Mice lacking the α7 subunit have impaired trace eye-blink conditioning.

“Mice lacking the α7 subunit have been shown to have impaired trace eye-blink conditioning (Brown et al. 2010).”

• cites Brown et al. 2010 sourceSupported

nAChRs play a role in maturation of circuits important for attention during development.

“many studies have shown a role for nAChRs in maturation of circuits important for attention during development (reviewed in Heath and Picciotto 2009).”

• cites Heath and Picciotto 2009 sourceSupported

Deletion of the β4 nAChR subunit from either POMC or NPY neurons is sufficient to attenuate nicotinic-induced decreases in food intake.

“deletion of the β4 nAChR subunit from either subtype is sufficient to attenuate nicotinic-induced decreases in food intake (Calarco et al. 2018).”

• cites Calarco et al. 2018 sourcePartly supported

  The Results section (page not provided) reports that β4 knockdown in POMC or AgRP neurons blunted the decrease in food intake caused by nicotine. The cited study used knockdown, not deletion, and tested AgRP neurons rather than identifying the tested population as NPY neurons. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Currents mediated through α5/β2 nAChRs are maximal in the early postnatal period.

“Electrophysiological studies have shown that currents mediated through α5/β2 Ã nAChRs are maximal in the early postnatal period (Kassam et al. 2008).”

• cites Kassam et al. 2008 sourcePartly supported

  The section “Nicotinic currents in layer VI pyramidal neurons change across development” reports that currents in rat prefrontal cortical neurons were highest in the first postnatal month. The paper separately says pharmacological results suggest involvement of α5-containing α4β2 receptors; it does not establish that the measured developmental peak was specifically a peak in currents mediated by that receptor subtype. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Withdrawal from binge eating increases acetylcholine release in the NAc.

“withdrawal from binge eating increases acetylcholine release in the NAc (Avena et al. 2008).”

• cites Avena et al. 2008 sourcePartly supported

  The Results report increased extracellular acetylcholine in the nucleus accumbens after 24–36 hours of fasting in rats that had binged on sucrose and chow. The Abstract interprets the fasting state as resembling opiate-like withdrawal. The claim omits those limits and states the effect for withdrawal from binge eating generally. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

In a slice preparation, the effects of nicotine on firing of POMC neurons persist longer than firing of NPY neurons.

“in a slice preparation, the effects of nicotine on firing of POMC neurons persist longer than firing of NPY neurons (Parikh et al. 2007(Parikh et al. , 2008))”

• cites Parikh et al. 2007 sourceNot checked — no full text of the source
• cites Parikh et al. 2008 sourceCould not verify

  The Methods describe in vivo recordings of cholinergic signals in the medial prefrontal cortex, and the Discussion compares the decay of nicotine- and ABT-089-evoked signals. Searches for POMC, NPY, and slice-based neuronal firing found no passage comparing nicotine’s effects on those neurons. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

At the circuit level, stimulation of nAChRs shifts the balance toward neuronal patterns that signal satiety.

“showing that at the circuit level, stimulation of nAChRs shifts the balance toward neuronal patterns that signal satiety (Calarco and Picciotto 2020).”

• cites Calarco and Picciotto 2020 sourcePartly supported

  The 'nAChR Signaling in the ARC' section reports that nicotine increases firing in POMC neurons, which are associated with reduced feeding. But it also increases firing in AgRP neurons, and the paper presents its explanation for reduced food intake as a hypothesis—not a demonstrated shift toward a satiety-associated neuronal pattern. The Figure 3 caption likewise describes both populations as activated by nicotine. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Local infusion of a nicotinic agonist into the VTA, but not the NAc, is sufficient for nicotine place preference in rats.

“This is consistent with previous studies suggesting that nAChRs within the VTA are critical for nicotine reward, because local infusion of a nicotinic agonist into the VTA, but not the NAc, is sufficient for nicotine place preference in the rat (Museo and Wise 1994).”

• cites Museo and Wise 1994 sourceNot checked — no full text of the source

Molecular genetic studies support that α4/α6/β2* nAChRs on DA neurons in the VTA are essential for nicotine reinforcement.

“Thus, molecular genetic studies support the idea that α4/α6/β2 Ã nAChRs on DA neurons in the VTA are essential for nicotine reinforcement.”

nAChRs containing the β2 subunit are essential for nicotine to depolarize DA cell bodies in the VTA and increase their firing rate.

“Electrophysiological studies have shown that nAChRs containing the β2 subunit are essential for the ability of nicotine to depolarize DA cell bodies in the VTA and to increase their firing rate (Picciotto et al. 1998;Zhou et al. 2001).”

• cites Picciotto et al. 1998 sourceNot checked — no full text of the source
• cites Zhou et al. 2001 sourceNot checked — no full text of the source

Gain-of-function studies of α6 coupled with α4 knockout show that the predominant receptor mediating DA release from VTA neurons is the α4/α6/β2* subtype.

“Gain-of-function studies of the α6 subunit, coupled with α4 subunit knockout show that the predominant receptor mediating DA release from VTA neurons are of the α4/α6/ β2 Ã subtype (Engle et al. 2013).”

• cites Engle et al. 2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

In a slice preparation, nicotine can potentiate glutamate input to DA neurons through α7 nAChRs, resulting in long-term potentiation of those inputs.

“In a slice preparation, nicotine can potentiate glutamate input to DA neurons through α7 nAChRs, resulting in long-term potentiation of those inputs (Mansvelder and McGehee 2000).”

• cites Mansvelder and McGehee 2000 sourceNot checked — no full text of the source

Postsynaptic depolarization of DA neurons is essential for behaviors related to nicotine reward and reinforcement such as place preference and self-administration.

“Evidence from mouse genetic models with knockout or mutations of nAChR subunits suggests that the postsynaptic depolarization of DA neurons is essential for behaviors related to nicotine reward and reinforcement such as nicotine place preference and self-administration.”

Disruption of α5* nAChR signaling diminishes the stimulatory effects of nicotine on MHb-IPN activity and thereby permits greater nicotine consumption.

“Hence, disruption of α5 Ã nAChR signaling diminishes the stimulatory effects of nicotine on MHb-IPN activity, and thereby permits consumption of greater quantities of nicotine.”

Nicotine-induced activation of the MHb-IPN pathway produces a negative motivational signal that limits further nicotine intake.

“Nicotineinduced activation of the MHb-IPN pathway results in a negative motivational signal that serves to limit further nicotine intake.”

Nicotine activates the MHb-IPN pathway through stimulatory effects on α5* nAChRs.

“Taken together, these findings suggest that nicotine activates the MHb-IPN pathway through stimulatory effects on α5 Ã nAChRs.”

Approximately 90%-100% of MHb neurons express α3, α4, α5, β2, and β4 nAChR subunits.

“Indeed, approximately 90%-100% of MHb neurons express α3, α4, α5, β2, and β4 nAChR subunits (Sheffield et al. 2000)”

• cites Sheffield et al. 2000 sourceNot checked — no full text of the source

Overexpression of β4* nAChRs in mice using BAC transgenic technology resulted in greatly diminished sensitivity to the reinforcing properties of orally consumed nicotine solutions and far less consumption than wild-type mice.

“Specifically, overexpression of β4 Ã nAChRs in mice using BAC transgenic technology resulted in greatly diminished sensitivity to the reinforcing properties of orally consumed nicotine solutions and far less consumption of the drug than wild-type mice (Frahm et al. 2011).”

• cites Frahm et al. 2011 sourceNot checked — no full text of the source

The MHb contains some of the highest densities of nicotine-binding sites in the brain.

“The MHb contains some of the highest densities of nicotine-binding sites in brain (Mugnaini et al. 2002).”

• cites Mugnaini et al. 2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

nAChRs containing α5, α3, and/or α4 subunits, densely expressed in the MHb-IPN pathway, regulate addiction-related actions of nicotine.

“The above findings suggest that nAChRs containing α5, α3, and/or α4 nAChR subunits, densely expressed in the MHb-IPN pathway, regulate addiction-related actions of nicotine.”

The highest densities of α5, α3, and α4 nAChR subunit expression in the brain are detected in the MHb and/or IPN.

“In particular, the highest densities of α5, α3, and α4 nAChR subunits expression in brain are detected in MHb and/or IPN (De Biasi and Salas 2008).”

• cites De Biasi and Salas 2008 sourceNot checked — no full text of the source

β4* nAChRs in the MHb-IPN pathway regulate sensitivity to the aversive effects of nicotine that control the quantities consumed.

“This finding suggests that, similar to α5 Ã nAChRs, β4 Ã nAChRs in the MHb-IPN pathway also regulate sensitivity to the aversive effects of nicotine that control the quantities of the drug consumed.”

Withdrawal duration and severity predict relapse in abstinent human smokers.

“Indeed, withdrawal duration and severity predict relapse in abstinent human smokers (Piasecki et al. 1998(Piasecki et al. , 2000(Piasecki et al. , 2003)).”

• cites Piasecki et al. 1998 sourceNot checked — no full text of the source
• cites Piasecki et al. 2000 sourceNot checked — no full text of the source
• cites Piasecki et al. 2003 sourceNot checked — no full text of the source

The nicotine withdrawal syndrome in abstinent smokers comprises somatic and affective components.

“The nicotine withdrawal syndrome in abstinent smokers is comprised of”

• cites Parrott 1993 sourceNot checked — no full text of the source
• cites Doherty et al. 1995 sourceNot checked — no full text of the source
• cites Kenny and Markou 2001 sourceNot checked — no full text of the source

TCF7L2 acts downstream from GLP-1 receptor-mediated transmission to regulate the function of habenular nAChRs and thereby control nicotine intake.

“Taken together, these observations suggest TCF7L2 acts downstream from GLP-1 receptor-mediated transmission to regulate the function of habenular nAChRs and thereby control nicotine intake.”

• AssumptionRests on an assumption: GLP-1 receptors are Gs-coupled G-protein-coupled receptors that enhance cAMP production.
• AssumptionRests on an assumption: In pancreatic β cells, GLP-1-stimulated increases in cAMP cause phosphorylation and nuclear translocation of β-catenin, which dimerizes with TCF7L2.

Affective symptoms of nicotine withdrawal primarily include depressed mood with anhedonia, dysphoria, anxiety, irritability, difficulty concentrating, and craving.

“Affective symptoms primarily include depressed mood including anhedonia, dysphoria, anxiety, irritability, difficulty concentrating, and craving (Parrott 1993;Doherty et al. 1995;Kenny and Markou 2001).”

• cites Parrott 1993 sourceNot checked — no full text of the source
• cites Doherty et al. 1995 sourceNot checked — no full text of the source
• cites Kenny and Markou 2001 sourceNot checked — no full text of the source

GLP-1 released from NTS inputs to the IPN stimulates terminals of MHb cholinergic neurons to enhance excitatory transmission onto IPN neurons and inhibit nicotine intake.

“These findings suggest that GLP-1, released from NTS inputs to IPN, stimulates the terminals of MHb cholinergic neurons to enhance excitatory transmission onto IPN neurons to inhibit nicotine intake.”

Direct infusion of mecamylamine into the IPN, but not the VTA, of nicotine-dependent wild-type mice precipitated somatic withdrawal signs.

“Moreover, direct infusion of mecamylamine into the IPN, but not the VTA, of nicotinedependent wild-type mice precipitated the expression of somatic withdrawal signs (Salas et al. 2009).”

• cites Salas et al. 2009 sourceNot checked — no full text of the source

α5* and α2* nAChRs in the MHb-IPN pathway, and perhaps other subtypes enriched there, regulate the expression of somatic signs of nicotine withdrawal.

“This suggests that α5 Ã and α2 Ã nAChRs in the MHb-IPN pathway, and perhaps other nAChR subtypes enriched in this pathway, regulate the expression of somatic signs of nicotine withdrawal.”

α5 and α2 subunit knockout mice made dependent on nicotine did not show somatic signs of nicotine withdrawal when withdrawal was precipitated with mecamylamine.

“α5 and α2 subunit knockout mice that were dependent on nicotine (delivered through subcutaneously implanted osmotic minipumps) did not show somatic signs of nicotine withdrawal when withdrawal was precipitated with the nAChR antagonist mecamylamine (Salas et al. 2009).”

• cites Salas et al. 2009 sourceNot checked — no full text of the source

The most common somatic symptoms of nicotine withdrawal include bradycardia, gastrointestinal discomfort, and increased appetite.

“The most common somatic symptoms include bradycardia, gastrointestinal discomfort, and increased appetite.”

• cites Parrott 1993 sourceNot checked — no full text of the source
• cites Doherty et al. 1995 sourceNot checked — no full text of the source
• cites Kenny and Markou 2001 sourceNot checked — no full text of the source

Some of the highest densities of GLP-1 receptor binding sites in the brain are detected in the IPN.

“Notably, some of the highest densities of GLP-1 receptor binding sites in the brain are detected in the IPN (Göke et al. 1995).”

• cites Göke et al. 1995Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

α5 and β4, and perhaps α2 and α3, nAChRs enriched in the MHb-IPN pathway play a key role in regulating nicotine reinforcement and the expression of nicotine withdrawal syndrome in nicotine-dependent rodents.

“The above findings support a key role for α5 and β4, and perhaps also α2 and α3 nAChRs, which are enriched in the MHb-IPN pathway in regulating nicotine reinforcement and the expression of the nicotine withdrawal syndrome in nicotine-dependent rodents.”

Nicotine stimulates GLP-1 neurons in the NTS via α5* nAChRs, which in turn enhances activity of the MHb-IPN pathway to inhibit nicotine intake.

“Taken together, these findings suggest that nicotine stimulates GLP-1 neurons in NTS via a5 Ã nAChRs, which in turn enhances the activity of the MHb-IPN pathway to inhibit nicotine intake.”

GLP-1 released from NTS neurons may regulate activity of the MHb-IPN pathway to control nicotine intake.

“This suggests that GLP-1 released from NTS neurons may regulate activity of the MHb-IPN pathway to control nicotine intake.”

The behavioral effects of increased hippocampal ACh signaling mirror the increased depressive symptoms observed in human subjects administered an AChE antagonist.

“This mirrors the increased depressive symptoms observed in human subjects administered an AChE antagonist (Risch et al. 1981)”

• cites Risch et al. 1981Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Stimulation of α5β4 nAChRs is important for the anxiogenic effects of nicotine.

“These data suggest that stimulation of α5β4 Ã nAChRs is important for the anxiogenic effects of nicotine.”

Mecamylamine is effective as an add-on medication in depressed human subjects who are nonresponsive to an SSRI.

“is effective as an add-on medication in depressed human subjects who are nonresponsive to a selective serotonin reuptake inhibitor (SSRI) (George et al. 2008)”

• cites George et al. 2008 sourceNot checked — no full text of the source

The anxiolytic and anxiogenic effects of nicotine are likely mediated by different nAChR subtypes.

“and these effects are likely to depend on different nAChR subtypes.”

Mice lacking the α7 nAChR subunit are resistant to the antidepressant-like effects of mecamylamine.

“mice lacking the α7 subunit are also resistant to the antidepressant-like effects of mecamylamine (Rabenstein et al. 2006)”

• cites Rabenstein et al. 2006 sourceNot checked — no full text of the source

β2 nAChRs are critical for the antidepressant-like effects of nicotinic drugs.

“suggesting that β2 Ã nAChRs are critical for the antidepressant-like effects of nicotinic drugs.”

ACh-serotonin interactions can contribute to dysphoric effects of ACh signaling mediated through the hippocampus.

“suggesting that ACh-serotonin interactions can contribute to dysphoric effects of ACh signaling mediated through this structure.”

Other nAChR subtypes may also contribute to the antidepressant-like effects of nicotinic drugs.

“suggesting that other nAChR subtypes may also contribute to the antidepressant-like effects of nicotinic drugs”

Activation as well as inhibition of nAChRs can show antidepressant-like effects.

“and that activation as well as inhibition of nAChRs can show antidepressant-like effects.”

Mecamylamine has antidepressant-like effects in mice.

“the nicotinic antagonist mecamylamine has antidepressantlike effects in mice (Caldarone et al. 2004;Rabenstein et al. 2006;Andreasen et al. 2009)”

• cites Caldarone et al. 2004 sourceNot checked — no full text of the source
• cites Rabenstein et al. 2006 sourceNot checked — no full text of the source
• cites Andreasen et al. 2009 sourceNot checked — no full text of the source

nAChR subtypes regulate baseline activity of the basolateral amygdala (BLA).

“nAChR subtypes regulate baseline activity of the basolateral amygdala (BLA)”

Activation of nAChRs decreases depression-like behavior in the Flinders-sensitive rat model.

“suggesting that activation of nAChRs de-creases depression-like behavior in this model (Tizabi et al. 2000)”

• cites Tizabi et al. 2000 sourceNot checked — no full text of the source

Acute nicotine administration is antidepressant-like in the forced swim test in Flinders-sensitive rats.

“acute nicotine administration is antidepressant-like in the forced swim test”

• cites Tizabi et al. 2000 sourceNot checked — no full text of the source

The cycles of nAChR activation and desensitization experienced by smokers may result in fluctuations in depressive symptoms throughout the day.

“so the cycles of nAChR activation and desensitization experienced by smokers may result in fluctuations in depressive symptoms throughout the day.”

5HT1a serotonin receptors in the hippocampus are required for antidepressant-like effects of nicotinic compounds.

“5HT1a serotonin receptors in hippocampus are required for antidepressantlike effects of nicotinic compounds (Mineur et al. 2015)”

• cites Mineur et al. 2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Decreasing nAChR activity in the BLA can induce resilience to stress, even in animals with no manipulation of ACh activity.

“and decreasing their activity can induce resilience to stress, even in animals with no manipulation of ACh activity.”

Some estimates suggest that about 44% of cigarettes are sold to individuals with a current psychiatric condition.

“and some estimates suggest that ∼44% of cigarettes are sold to individuals with a current psychiatric condition (Lasser et al. 2000).”

• cites Lasser et al. 2000 sourceNot checked — no full text of the source

Inhibition of nAChRs in some neuronal subtypes or brain areas and activation in others may contribute to an antidepressant-like effect of nicotinic drugs.

“These data suggest that inhibition of nAChRs in some neuronal subtypes or brain areas and activation in others may contribute to an antidepressant-like effect of nicotinic drugs”

β2 knockout mice show decreased depression-like behavior at baseline.

“and these knockout mice show decreased depression-like behavior at baseline”

Local knockdown of the α7 nAChR subunit in the hippocampus greatly attenuated the anxiogenic and social interaction phenotypes induced by AChE blockade.

“Local knockdown of the α7 nAChR subunit in the hippocampus greatly attenuated the anxiogenic and social interaction phenotypes induced by AChE blockade (Mineur et al. 2018a)”

• cites Mineur et al. 2018aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

The antidepressant-like effect of acute nicotine in Flinders-sensitive rats can be blocked by mecamylamine.

“this effect can be blocked by the nicotinic antagonist mecamylamine”

• cites Tizabi et al. 2000 sourceNot checked — no full text of the source

Expression of β2 nAChRs in the BLA is necessary for the antidepressant-like effects of the noradrenergic agonist guanfacine.

“Expression of β2 Ã nAChRs in the BLA is necessary for the antidepressant-like effects of the noradrenergic agonist guanfacine”

• cites Mineur et al. 2018bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

ACh-norepinephrine interactions are important for regulation of BLA activity and associated stress-induced behaviors.

“suggesting that ACh-norepinephrine interactions are important for regulation of BLA activity and associated stress-induced behaviors (Mineur et al. 2018b).”

• cites Mineur et al. 2018bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

β4 nAChRs on proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus are necessary for the appetite-suppressing effects of nicotine.

“β4 Ã nAChRs on proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus are necessary for the appetite-suppressing effects of nicotine (Mineur et al. 2011b).”

• cites Mineur et al. 2011bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Disrupting normal acetylcholine signaling through these nAChRs during a critical period has lasting effects on the function of the corticothalamic circuit in passive avoidance behavior.

“suggesting that disrupting normal acetylcholine signaling through these nAChRs during a critical period has lasting effects on the function of the corticothalamic circuit in passive avoidance behavior.”

β2 nAChRs in the prelimbic medial prefrontal cortex are important for normal performance of the 5-choice serial reaction time task measuring visual attention.

“Studies using knockout mice with lentiviralmediated reexpression have shown that β2 Ã nAChRs in the prelimbic medial prefrontal cortex (mPFC) are important for normal performance of the 5-choice serial reaction time task measuring visual attention.”

• AssumptionRests on an assumption: β2 nAChRs in the prelimbic medial prefrontal cortex are important for normal performance of the 5-choice serial reaction time task measuring visual attention.

Nicotine decreases feeding in animal models.

“nicotine decreases feeding in animal models (Grunberg et al. 1987)”

• cites Grunberg et al. 1987 sourceNot checked — no full text of the source

α7 nAChRs are implicated in prepulse inhibition, a physiological marker associated with schizophrenia.

“Genetic and functional studies have implicated α7 nAChRs in prepulse inhibition, a physiological marker associated with schizophrenia (Leonard et al. 2000;Freedman et al. 2003).”

• cites Leonard et al. 2000 sourceNot checked — no full text of the source
• cites Freedman et al. 2003 sourceNot checked — no full text of the source

β2α4α6 nAChRs are critical for nicotine reward and reinforcement.

“Whereas β2α4α6 Ã nAChRs are critical for nicotine reward and reinforcement”

• AssumptionRests on an assumption: β2α4α6 nAChRs are critical for nicotine reward and reinforcement.

Nicotine and nicotinic drugs can improve attention in individuals with schizophrenia.

“and individuals with schizophrenia (Sacco et al. 2004).”

• cites Sacco et al. 2004Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

After control subjects quit smoking and transition past the acute withdrawal period, their working memory function improves compared with when they were smoking.

“after control subjects quit smoking and transition past the acute withdrawal period, their working memory function improves compared with when they were smoking (George et al. 2002).”

• cites George et al. 2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Individuals with schizophrenia show impaired performance once they quit smoking.

“individuals with schizophrenia show impaired performance once they quit smoking (George et al. 2002).”

• cites George et al. 2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

The principal reason cited by female teenagers for why they smoke is weight control.

“the principal reason cited by female teenagers for why they smoke is weight control (Voorhees et al. 2002).”

• cites Voorhees et al. 2002 sourceNot checked — no full text of the source

The anorexic effects of smoking have been well-documented in human subjects.

“The anorexic effects of smoking have been welldocumented in human subjects”

• AssumptionRests on an assumption: The anorexic effects of smoking have been well-documented in human subjects.

The nicotine in tobacco is important for the effects of smoking on appetite.

“suggesting that the nicotine in tobacco is important for the effects of smoking on appetite.”

There are a number of nAChR subtypes expressed in the hypothalamus.

“There are a number of nAChR subtypes expressed in the hypothalamus (Jo et al. 2002(Jo et al. , 2005))”

• cites Jo et al. 2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Jo et al. 2005Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Increased ACh signaling can lead to symptoms of depression and anxiety in human subjects and mouse models.

“The observation that increased ACh signaling can lead to symptoms of depression and anxiety in human subjects and mouse models”

Nicotine and nicotinic drugs can improve attention in control subjects.

“nicotine and nicotinic drugs can improve attention in control subjects (Rusted and Warburton 1992)”

• cites Rusted and Warburton 1992 sourceNot checked — no full text of the source

Incorporation of α6 and β3 nAChR subunits in α4β2 nAChRs in the mesoaccumbens pathway gives rise to an nAChR subtype (α4α6β2β3) that appears to play a particularly important role in nicotine reinforcement.

“incorporation of α6 and β3 nAChR subunits in α4β2 Ã nAChRs in the mesoaccumbens pathway gives rise to an nAChR subtype (α4α6β2β3 Ã ) that appears to play a particularly important role in nicotine reinforcement.”

High-affinity α4β2 nAChRs play a key role in the behavioral actions of nicotine that contribute to the development of tobacco dependence, including its effects on brain circuitries involved in reinforcement, mood, attention, and food consumption.

“The high-affinity α4β2 Ã nAChRs play a key role in the behavioral actions of nicotine that contribute to the development of tobacco dependence, including its effects on brain circuitries involved in reinforcement, mood, attention, and food consumption.”

The DA system is important for the hedonic value of both drugs of abuse, like nicotine, and palatable foods.

“The DA system is important for the hedonic value of both drugs of abuse, like nicotine, and palatable foods (Kenny 2011).”

• cites Kenny 2011 sourceNot checked — no full text of the source

nAChRs in the mesolimbic DA system may be more important for the motivation to work for food.

“nAChRs in the mesolimbic DA system may be more important for the motivation to work for food.”

β4 nAChRs also play an important role in appetite regulation, particularly the inhibitory effects of nicotine on appetite that underlie the anorectic effects of tobacco smoke.

“β4 Ã nAChRs also play an important role in appetite regulation, particularly the inhibitory effects of nicotine on appetite that underlie the anorectic effects of tobacco smoke.”

Food or sugar intake can increase acetylcholine release in the VTA.

“Food or sugar intake can increase acetylcholine release in the VTA (Hajnal et al. 1998;Rada et al. 2000)”

• cites Hajnal et al. 1998 sourceNot checked — no full text of the source
• cites Rada et al. 2000 sourceNot checked — no full text of the source

Blocking α7 nicotinic AChRs in the VTA can decrease food seeking.

“blocking α7 nicotinic AChRs in the VTA can decrease food seeking (Schilström et al. 1998).”

• cites Schilström et al. 1998 sourceNot checked — no full text of the source

β4 nAChRs on POMC neurons can signal satiety.

“Although β4 Ã nAChRs on POMC neurons can signal satiety”

• AssumptionRests on an assumption: β4 nAChRs on POMC neurons can signal satiety.