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Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states
Open accessAbstract
The co-morbidity between smoking and mood disorders is striking. Preclinical and clinical studies of nicotinic effects on mood, anxiety, aggression, and related behaviors, such as irritability and agitation, suggest that smokers may use the nicotine in tobacco products as an attempt to self-medicate symptoms of affective disorders. The role of nicotinic acetylcholine receptors (nAChRs) in circuits regulating mood and anxiety are beginning to be elucidated in animal models, but the mechanisms underlying the effects of nicotine on aggression-related behavioral states (ARBS) are still not understood. Clinical trials of nicotine or nicotinic medications for neurological and psychiatric disorders have often found effects of nicotinic medications on ARBS, but few trials have studied these outcomes systematically. Similarly, the increase in ARBS resulting from smoking cessation can be resolved by nicotinic agents, but the effects of nicotinic medications on these types of mental states and behaviors in non-smokers are less well understood. Here we review the literature on the role of nAChRs in regulating mood and anxiety, and subsequently on the closely related construct of ARBS. We suggest avenues for future study to identify how nAChRs and nicotinic agents may play a role in these clinically important areas.
Overview
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Written from the paper’s full text.
TL;DR
This review synthesizes preclinical and clinical evidence that nicotinic acetylcholine receptors (nAChRs) regulate mood and anxiety and the closely related construct of aggression-related behavioral states (ARBS), suggesting smokers may use nicotine to self-medicate affective symptoms. It argues nicotinic agents may reduce ARBS across diagnoses, but mechanisms and whether agonists or antagonists are optimal remain unresolved.
Key findings
- Preclinical work indicates that decreasing α4β2* nAChR signaling can improve depression-like behaviors, that nAChR antagonists or partial agonists can potentiate SSRI/NRI effects, and that β2* nAChRs are required for antidepressant efficacy of at least one antidepressant; nicotine reduces aggression in many rat paradigms, with effects blocked by mecamylamine but not peripheral blockade by hexamethonium, while mouse results vary by strain and paradigm.
- Clinical imaging shows β2* nAChR availability is greatly decreased in actively depressed patients and intermediate in remitted subjects, suggesting a possible depression biomarker; nicotine can improve depressive symptoms even in non-smokers, and withdrawal is associated with anxiety, irritability, and aggression.
- In a double-blind, placebo-controlled trial of transdermal nicotine in adult smokers with schizophrenia, agitation decreased 33% on the Agitated Behavior Scale versus 23% for placebo, with greater reductions on the PANSS excited component; in ADHD, a small study (n = 17) found no effect on agitation/aggression subscales, while a larger study (n = 40) found post-hoc significant improvement in irritability only.
- A mecamylamine trial in Tourette’s syndrome (n = 61) found no overall symptom difference from placebo but a significant decrease in “sudden mood changes”; in an ICU prospective trial (n = 144), smokers had an almost doubled rate of agitation versus controls when nicotine replacement was not permitted.
Methods
- Narrative review of preclinical and clinical literature on nAChRs in mood, anxiety, and ARBS; no primary data collection.
- Evidence includes animal models (rodent and cat aggression paradigms, knockout mice, pharmacological studies) and human studies (clinical trials, case series, imaging, post-mortem, and nicotine withdrawal studies).
- Main analysis is qualitative synthesis; no systematic search strategy, meta-analysis, or formal risk-of-bias assessment is described.
Limitations
- The paper states that mechanisms underlying nicotine’s effects on ARBS are still not understood, that few clinical trials have studied ARBS outcomes systematically, that effects in non-smokers are less well understood, and that current clinical literature does little to clarify whether nicotinic agonists or antagonists are most helpful.
- The paper notes that many supporting clinical studies are small and uncontrolled case series, and some findings are secondary, post-hoc, or anecdotal.
- Evident from the text: as a narrative review, it cannot quantify pooled effects or systematically appraise study quality; species, strain, and sex differences complicate interpretation, as the paper itself states.
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Claims the paper makes
93 Not checked yet · 25 Own interpretation · 5 No basis given
None of the sources cited for this claim have been checked yet.
In the paper
“Nicotine consumption through tobacco products is highly co-morbid with mood disorders, including depression, anxiety and irritability”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction
What the sources say
plaincorrelational- 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.
In the paper
“low dose chronic nicotine has a comparable effect to an antagonist of high affinity β2 subunit-containing (β2*) nAChRs in a conditioned emotional response task in mice (Anderson and Brunzell, 2012)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Anderson and Brunzell, 2012
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“These data suggest that a partial agonist, or a mix of agents with differing effects at heteromeric and homomeric nAChRs may be the most promising for developing nicotinic-based antidepressants”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
hedgedconditional- 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.
In the paper
“there is some evidence that nAChRs in the amygdala could be important for the antidepressant effect of nAChR blockade (Mineur et al., 2007)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Mineur et al., 2007 source
hedgedconditional- 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.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“decreasing amygdala cholinergic activity through α4β2* nAChR blockade could decrease stress reactivity and depression-like symptoms (LeDoux, 2003; Mineur et al., 2007)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
hedgedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“commonly used antidepressants can also act as α4β2* nAChR antagonists in cell-based assays (Shytle et al., 2002; Slemmer et al., 2000)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
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.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“the effects of selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs) in models of depression-like behaviors can be potentiated by nAChR antagonists or partial agonists”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Andreasen et al., 2009
- Not checked yetcites Andreasen and Redrobe, 2009
- Not checked yetcites Rollema et al., 2009 source
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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“functional β4 nAChRs are required for the full effect of buproprion, an atypical antidepressant (Radhakrishnan et al., 2013)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Radhakrishnan et al., 2013 source
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.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“increased signaling at α7 nAChRs in combination with therapies that increase serotonin signaling can also improve performance in tests of antidepressant efficacy (Andreasen et al., 2012; Andreasen et al., 2013)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“β2* nAChRs are required for antidepressant efficacy of at least one antidepressant medication (Caldarone et al., 2004)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Caldarone et al., 2004 source
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.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 14
- It may state two separate claims as one. 43
In the paper
“the overall incidence of smoking in depressed patients is twice as high as in the general population (Glassman et al., 1990)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction
What the sources say
- Not checked yetcites Glassman et al., 1990 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This phenomenon could also underlie the cyclical mood dysregulation experienced by smokers between smoking episodes, and could therefore perpetuate smoking behavior (Watkins et al., 2000).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Watkins et al., 2000 source
hedgedconditional- 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.
- Based: passes — The paper gives a reason why it holds.
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
“because nicotine can both activate and desensitize different nAChR subtypes, resulting in differential modulation of many brain circuits, the net effect of nicotine on mood will depend on the integration of multiple nicotinic signals”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“α4β2* nAChRs can be rapidly and persistently desensitized in the presence of nicotine, whereas α7 nAChRs can maintain their activity (Mansvelder et al., 2002)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Mansvelder et al., 2002 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“nAChRs are expressed on many cell types throughout the central nervous system (Han et al., 2000), and modulate multiple neurotransmitter systems”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Han et al., 2000 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Chronic nicotine exposure induces up-regulation of nAChRs, but also profound desensitization of these receptors in vitro (Fenster et al., 1997; Grady et al., 1994).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
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.
- Based: passes — The paper gives a reason why it holds.
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
“These studies suggest that limiting nAChR signaling through α4β2* nAChRs can lead to positive effects on mood symptoms, however other nAChRs also appear to be important for antidepressant responses.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
hedgeddirect- 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.
In the paper
“These data suggest there is decreased ACh signaling through some nAChR subtypes during ongoing smoking, but likely to be restored and potentially increased over time (because high affinity nAChRs are upregulated by chronic nicotine use as experienced by smokers (Fenster et al., 1999) as nicotine is cleared during withdrawal.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Fenster et al., 1999 source
hedgedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“smoking cessation and nicotine withdrawal can be accompanied by depressive episodes, stress-induced anger, and increased tension (al'Absi et al., 2007; Hatsukami et al., 1985)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction
What the sources say
- Not checked yetcites al'Absi et al., 2007 source
- Not checked yetcites Hatsukami et al., 1985
plainconditional- 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.
In the paper
“both nicotine and the nicotinic antagonist mecamylamine can increase serotonin release in the hippocampus (Kenny et al., 2000)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Kenny et al., 2000 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“while increased ACh transmission can increase behaviors related to depression in humans (Risch et al., 1980) and rodents (Mineur et al., 2013), the type of circuits/cell types that are modulated by ACh or nAChRs can have opposite effects on mood regulation, and the outcome on behavior depends on the sum of these effects.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“At baseline, β2−/− mice exhibit increased levels of norepinephrine, dopamine, serotonin, and acetylcholine within the prelimbic region of the PFC, yet display similar levels of aggression compared to control mice both before and after global norepinephrine depletion.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Coura et al., 2013 source
plain- 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.
In the paper
“increasing doses of nicotine not only reduced the proportion of fighting episodes in rats after footshock, but also replaced that behavior with posturing (an intermediate aggressive behavior)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Driscoll and Baettig, 1981
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In cats, nicotine reduced aggression in a dose-dependent manner in a rat-biting assay, and doses that were highly effective at reducing aggression did not cause changes in food intake, suggesting a specific effect on aggression (Berntson et al., 1976).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Berntson et al., 1976 source
hedgeddirect- 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.
In the paper
“We recently found that serotonin depletion could prevent antidepressant-like effects induced by the nicotinic partial agonist cytisine in the forced swim and the social defeat tests, while the effects of serotonergic drugs could be potentiated by this nicotinic compound (Mineur et al., 2014).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Mineur et al., 2014
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a single nicotine injection reduced aggression from baseline, and four days of repeated daily injection reduced aggression even further”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Silverman, 1971 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In rats, a hypothalamic “aggression area” (HAA) has been implicated in aggressive behavior by stimulation paradigms, and efferents from this region have been mapped, with substantial connection throughout the brain, including thalamic nuclei, septal nuclei, and the periaqueductal gray (Roeling et al., 1994).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Roeling et al., 1994 source
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Strain differences in the antidepressant effects of nicotinic agonists and antagonists have been identified (Andreasen and Redrobe, 2009) and strains of mice can show profoundly different behavioral responses to nicotine administration (Marks et al., 1983; Marks et al., 1986)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
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
“changes in nAChR signaling, and more specifically, decreasing nAChR activity, can facilitate monoamine transmission and this may mediate the ability of nicotinic drugs to alter depression-like behaviors”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
hedgedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“while the nicotinic antagonist mecamylamine can have antidepressant-like properties in mouse models (Picciotto et al., 2008; Picciotto et al., 2012), antidepressant effects of this drug are not observed in assays of rats (Tizabi et al., 2000)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
plain- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cats specifically reduced biting, an aggressive behavior, while pawing and cuffing, non-aggressive behaviors, remained stable or increased, supporting the idea that nicotine had specific effects on behaviors related to aggression.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Berntson et al., 1976 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a distinct region within the HAA, the ventrolateral subdivision of the ventromedial hypothalamic nucleus (VMHvl), was recently shown to be necessary and sufficient for offensive aggression in mice (Lin et al., 2011)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Lin et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“mice lacking β2* nAChRs in dopamine neurons of the VTA lack anxiolytic responses to nicotine and are insensitive to nicotine reward (McGranahan et al., 2011)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites McGranahan et al., 2011 source
plain- 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.
In the paper
“a finding that suggests aggression was modulated by the balance of monoamines and acetylcholine in the prelimbic cortex, and requires functional β2 nAChRs (Coura et al., 2013)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Coura et al., 2013 source
hedgeddirect- 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.
In the paper
“in an isolation-induced aggression model, one study found no effect of acute nicotine on aggression but an anti-aggressive effect of lobeline, an agent with complex pharmacological properties at nAChRs (Redolat et al., 2000)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Redolat et al., 2000 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“both chronic nicotine and the nicotinic antagonist mecamylamine can facilitate serotonin transmission in the hippocampus, while the effects of monoamine depletion can be partially reversed by nicotine administration and can lead to changes in anxiety-like behavior in the elevated plus maze (File et al., 2000a; File et al., 2000b; Fu et al., 1998; Kenny et al., 2000)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites File et al., 2000a
- Not checked yetcites File et al., 2000b
- Not checked yetcites Kenny et al., 2000 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“effects of nicotine in the muricide study did not stem from a general sedating effect, were not affected by peripheral nAChR blockade with hexamethonium, and were blocked by mecamylamine (Waldbillig, 1980)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Waldbillig, 1980 source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nicotine influences the rate of dorsal raphe nucleus (DRN) neuron firing, and can increase serotonin release in rat midbrain slices (Mihailescu et al., 1998), an effect that appears to be largely mediated by presynaptic enhancement of both norepinephrine (Li et al., 1998) and glutamate release (Garduno et al., 2012).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
hedgeddirect- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ARBS are observed across numerous neuropsychiatric disorders, including depressive, bipolar, psychotic, neurocognitive, neurodevelopmental, stress-related, substance use and personality disorders (American Psychiatric Association, 2013).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites American Psychiatric Association, 2013
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A second line of evidence comes from a number of studies describing the prominence of ARBS in the context of nicotine withdrawal (Lucidarme et al., 2010), and the tendency for these symptoms to resolve following administration of nicotine (Schechter, 2011).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“including evidence of involvement of serotonin disruption in humans in aggressive states and traits, but dopaminergic, norepinephrinergic, and GABAergic neurotransmission have all been implicated in aggression (Nelson and Trainor, 2007; Takahashi et al., 2012b; Yanowitch and Coccaro, 2011)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Preclinical studies of nicotine on mood, anxiety, and aggression-related behavioral states
What the sources say
- Not checked yetcites Nelson and Trainor, 2007
- Not checked yetcites Takahashi et al., 2012b
- Not checked yetcites Yanowitch and Coccaro, 2011
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Clinical data on the role of nicotine in anxiety is more complex, with the most consistent findings being the development of anxiety symptoms in the context of withdrawal, and the observation that these symptoms may improve with nicotine replacement (Picciotto et al., 2002).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Picciotto et al., 2002 source
hedgedconditional- 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.
- Based: passes — The paper gives a reason why it holds.
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
“more selective antagonists or partial agonists may decrease signaling through specific nAChR subtypes while sparing others, and may be more effective or well-tolerated”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
hedgedconditional- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nicotine delivered through skin patches can also improve mood in non-smokers (Salin-Pascual et al., 1995; Salin-Pascual et al., 1996), potentially through sustained desensitization of nAChRs (Mineur and Picciotto, 2010; Picciotto et al., 2008).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Salin-Pascual et al., 1995 source
- Not checked yetcites Salin-Pascual et al., 1996
- Not checked yetcites Mineur and Picciotto, 2010
plainconditional- 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.
- Based: passes — The paper gives a reason why it holds.
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
“raise the possibility that β2* nAChR availability could be a biomarker of depression, correlated with severity of the symptoms”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
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.
In the paper
“in patients with schizophrenia, in whom the construct of “urgency”, defined as the tendency to act rashly in the context of positive or negative emotion, correlated strongly with aggression, and was inversely correlated with functional connectivity in a cortical circuit believed to modulate impulsivity (Hoptman et al., 2014)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Hoptman et al., 2014 source
boostedcorrelational- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Clinical studies have demonstrated an increased rate of smoking in individuals with depression (Diwan et al., 1998), a tendency for depressive symptoms to develop in the context of smoking cessation (Laje et al., 2001), and the capacity for nicotine to improve depressive symptoms, even in non-smokers (McClernon et al., 2006; Salin-Pascual et al., 1996).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
boosteddirect- 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.
In the paper
“Recent imaging studies have shown that availability of β2* nAChRs for tracer binding was greatly decreased in actively depressed patients but was intermediate in remitted subjects (Saricicek et al., 2012).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Saricicek et al., 2012 source
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“similar compounds have shown promising effects in smaller clinical trials, and enhanced the effects of SSRIs in human depressed subjects (George et al., 2008; Philip et al., 2009)”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
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.
- Based: passes — The paper gives a reason why it holds.
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
“suggesting that a subset of patients may be more responsive to these medications or have an underlying alteration of cholinergic signaling”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
hedgedconditional- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Current clinical literature does little to clarify whether nicotinic agonists or antagonists are most helpful for treating ARBS.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Conclusions
plain- 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.
Probably not a substantial claim.
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
“Notably, these studies have occurred across a variety of diagnostic categories.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Conclusions
plain- 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.
Probably not a substantial claim.
In the paper
“This was spontaneously reported by parents, and was sufficiently convincing that treatment was continued in these cases.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Arnold et al., 2012 source
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“More recently, a larger study (n = 40) found on post-hoc analysis that patients in the treatment arm experienced a statistically significant improvement in irritability with no improvement in any of the other 12 measures on the POMS.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
plaindirectn = 40- 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.
- Based: passes — The paper gives a reason why it holds.
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
“However, changes in nAChRs could provide relevant biomarkers for at least a subset of depressive symptoms, and may help with the diagnosis and characterization of the pathophysiology of depression.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Conclusions
hedgedconditional- 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: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Nicotine withdrawal and its affective consequences have been studied extensively (Stoker and Markou, 2013), yet the effects of nicotine withdrawal on aggressive behavior needs further exploration both in animal models and in humans.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Stoker and Markou, 2013
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“but provided anecdotal evidence of decreased irritability in four cases.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Arnold et al., 2012 source
plaindirectn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“and we hypothesize that the ability of these agents to modulate mood and anxiety might be one mechanism underlying these effects.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Conclusions
hedgedconditional- Asserted: fails — The authors may not 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.
Probably not a substantial claim. The authors may not put it forward as true.
None of the sources cited for this claim have been checked yet.
In the paper
“These studies were both small and uncontrolled, but contribute to an increasing base of clinical data justifying further exploration of nicotinic agents for management of ARBS across a variety of diagnostic categories.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Rosin et al., 2001 source
- Not checked yetcites Carmel and Sheitman, 2007
plain- 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.
- Based: passes — The paper gives a reason why it holds.
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
“However, changes in nAChRs could provide relevant biomarkers for at least a subset of depressive symptoms, and may help with the diagnosis and characterization of the pathophysiology of depression.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Conclusions
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“The first small study (n = 17) found that although nicotine was effective for overall symptoms, it had no effect on subscales associated with agitation or aggression (Conners et al., 1996).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites Conners et al., 1996
plainn = 17- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The concept of nicotine withdrawal has been codified in the DSM-5 and irritability is described as a characteristic symptom (American Psychiatric Association, 2013).”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
What the sources say
- Not checked yetcites American Psychiatric Association, 2013
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“At least one way to interpret these findings is to suggest that nicotinic agents may reduce ARBS not by influencing the core symptoms of schizophrenia, but via a parallel mechanism that only becomes apparent in individuals with suprathreshold levels of aggression.”
§ Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states > Introduction > Effects of nicotine on mood, anxiety, and aggression-related behavioral states in human and clinical studies
hedgedconditionaln = 4- 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.
Probably not a substantial claim.
The authors state this as an assumption.
The mechanisms mediating the connection between smoking and mood alterations are not yet understood.
“The underlying mechanisms mediating the connection between smoking and mood alterations are not yet understood, however.”
The authors state this as an assumption.
The mechanisms underlying the effects of nicotine on aggression-related behavioral states are still not understood.
“but the mechanisms underlying the effects of nicotine on aggression-related behavioral states (ARBS) are still not understood”
The authors state this as an assumption.
The effects of nicotinic medications on ARBS in non-smokers are less well understood.
“but the effects of nicotinic medications on these types of mental states and behaviors in non-smokers are less well understood”
The paper relies on this without support.
Many conditions involving impulsive aggression are chronic disorders that require long-term treatment.
“In addition, many conditions involving impulsive aggression are chronic disorders that require long-term treatment, such as neurodevelopmental or neurodegenerative disorders.”
The paper relies on this without support.
There is a lack of currently available agents to effectively treat aggression, irritability, and agitation without significant side effects.
“Despite the complexity, the lack of currently available agents to effectively treat aggression, irritability, and agitation without significant side effects means that further study in this promising area is strongly indicated.”
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
“antagonism at the nAChR in the amygdala reduces fear‐related behavior”
From The Pathway to Proof-of-Concept for BNC210, a Negative Allosteric Modulator of the Alpha-7 Nicotinic Acetylcholine Receptor (nAChR), for Treatment of Psychiatric Disease (2026) · cites this paper as [2]
Experimental — accuracy not yet measured
Citations
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Metadata
- Authors
- Picciotto, M. R., Lewis, A. S., van Schalkwyk, G. I., & Mineur, Y. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Picciotto, Marina R.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 96
- Issue
- Pt B
- Pages
- 235-243
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC4486625
- OpenAlex
- W1969972941
- Semantic Scholar
- 32f08831c6a19ce6d7602ffbde36908f6094129b
- Cited by
- 157
- References
- 154
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 10 · 2023: 15 · 2022: 17 · 2021: 11 · 2020: 17 · 2019: 18 · 2018: 14 · 2017: 16 · 2016: 7 · 2015: 8
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH077681, MH19961, MH014276, DA033945, DA14241)
- 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 › Neuroscience and Neuropharmacology Research
- Keywords
- nicotinic acetylcholine receptors, nicotine, mood regulation, anxiety regulation, irritability, agitation, self-medication, smoking cessation, nicotinic agonists, psychiatric comorbidity
- MeSH terms
- Affect, Aggression, Animals, Anxiety, Clinical Trials as Topic, Humans, Nicotine, Receptors, Nicotinic, Substance Withdrawal Syndrome, Tobacco Use Disorder, Nicotinic Agonists
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