The DOI matches its Crossref record; 57 of the 64 references it cites were found in a registry or an index; 5 of the 36 sources its claims cite were checked for support.
Human Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers
Open accessAbstract
Nicotine, the addictive chemical in tobacco smoke, initiates its actions in brain through nicotinic acetylcholine receptors (nAChRs). In particular, nAChRs containing β 2-subunits (β 2*-nAChRs) the most prevalent subtype, mediate the reinforcing properties of nicotine. We hypothesized that abnormal numbers of β 2*-nAChRs during early abstinence contribute to the perpetuation of addiction to tobacco smoking. Using molecular imaging, specifically single-photon emission computed tomography with the nAChR agonist radiotracer [123 I]5-IA-85380 ([123 I]5-IA), we imaged β 2*-nAChR availability in human smokers. First, using nonhuman primates treated chronically with nicotine, we estimated the time interval necessary for smokers to abstain from smoking so that residual nicotine would not interfere with [123 I]5-IA binding to the β 2*-nAChR as ∼7 d. Thus, we imaged human smokers at 6.8 ± 1.9 d (mean ± SD) of abstinence. Abstinence was confirmed by daily assessments of urinary cotinine and expired carbon monoxide levels. In smokers, [123 I]5-IA uptake was significantly higher throughout the cerebral cortex (26–36%) and in the striatum (27%) than in nonsmokers, suggesting higher β 2*-nAChR in recently abstinent smokers. β 2*-nAChR availability in recently abstinent smokers correlated with the days since last cigarette and the urge to smoke to relieve withdrawal symptoms but not the severity of nicotine dependence, severity of nicotine withdrawal, or the desire to smoke. Higher brain β 2*-nAChR during early abstinence indicates that, when smokers quit smoking, they do so in the face of a significant increase in the receptors normally activated by nicotine. Greater β 2*-nAChR availability during early abstinence may impact the ability of smokers to maintain abstinence.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Using [123I]5-IA SPECT, this study found that human smokers in early abstinence have higher brain β2*-nicotinic acetylcholine receptor availability than nonsmokers. The authors suggest this upregulation may influence the ability to maintain smoking abstinence.
Key findings
- Smokers imaged after 6.8 ± 1.9 d of abstinence showed significantly higher [123I]5-IA uptake than nonsmokers throughout cerebral cortex (26–36%) and in striatum (27%); region-of-interest analyses also showed higher uptake in cerebellum (25.2%) but not thalamus (8.7%, p = 0.1651).
- In nonhuman primates, [123I]5-IA binding decreased 41–65% after 1–2 d of nicotine withdrawal, then increased 240–276% after 7 d of withdrawal, supporting an approximately 7 d abstinence interval before human imaging.
- In smokers, β2*-nAChR availability correlated with days since last cigarette and with urge to smoke to relieve withdrawal symptoms, but not with severity of nicotine dependence, severity of nicotine withdrawal, or desire to smoke.
Methods
- Two male adolescent rhesus macaques received oral nicotine dose escalation and were imaged with [123I]5-IA SPECT at baseline, after 6 weeks of nicotine plus 1–2 d withdrawal, and after 8 weeks of nicotine plus 7 d withdrawal.
- Human smokers (n = 16) and nonsmokers (n = 16) matched on age and sex were imaged with [123I]5-IA SPECT using a bolus-plus-constant-infusion paradigm; smokers abstained for 6.8 ± 1.9 d, confirmed by urinary cotinine and expired carbon monoxide.
- Regional β2*-nAChR availability was measured as V_T′ using MRI-guided regions of interest and voxel-based SPM2 analyses; group differences used MANOVA and t tests, and clinical correlations used Pearson’s correlation.
Limitations
- The paper states that a species difference cannot be ruled out because nonhuman primates were male adolescents while human smokers were male and female adults, and it notes that interindividual variability in nicotine metabolism/CYP2A6 is expected.
- The paper reports that technical problems precluded determining plasma levels in one monkey at 6 weeks/2 d withdrawal.
- Evident from the text: human samples were small (n = 16 per group), cross-sectional, and correlational; V_T′ interpretation assumes no change in affinity and no difference in nondisplaceable uptake.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
5 of 36 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Because nicotine competes with [ 123 I]5-IA binding for binding to nAChRs (Mukhin et al., 2000)”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Introduction
What the sources say
- Could not verifycites Mukhin et al., 2000 sourceExperimental — accuracy not yet measured
The available indexed passages (no section or page labels) list nicotine and 5-iodo-A-85380 as receptor ligands, but do not describe nicotine competing with [123I]5-IA for binding. Searches for nicotine displacement, inhibition, and competitive binding returned no passage addressing that relationship. (LLM, conf=0.70)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“With the recent development of [ 123 I]5-IA-85380 ([ 123 I]5-IA), a radioligand that has specificity for the agonist binding site on  2 *- nAChRs (Musachio et al., 1998(Musachio et al., , 1999;;Horti et al., 1999)”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Introduction
What the sources say
- Partly supportedcites Musachio et al., 1998 sourceExperimental — accuracy not yet measured
The Results (page not provided) show that nAChR agonists inhibited [125I]5-IA binding in mouse brain, and the Discussion reports specificity for central nAChRs. However, the Discussion only predicts selectivity for the α4β2 subtype; it does not establish specificity for the agonist binding site on β2*-nAChRs. (LLM, conf=0.85)
- Partly supportedcites Musachio et al., 1999 sourceExperimental — accuracy not yet measured
The Discussion (page not provided) describes [123I]5-IA as a highly specific probe for central nAChRs and reports that the agonist cytisine blocked its uptake in baboon brain. It does not establish specificity for the agonist binding site on β2*-nAChRs; it says only that radioiodinated 5-IA might be more selective for the α4β2 subtype. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites Horti et al., 1999 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“but instead appears to be attributable to occupancy of the nicotine binding site that bridges the ␣/ subunit interface of the nAChR in an immature, low-affinity conformation that facilitates glycosylation and maturation of the ␣ 4  2 nAChR to a more stable conformation with higher affinity for nicotine (Darsow et al., 2005;Sallette et al., 2005).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Not checked — no full text of the sourcecites Darsow et al., 2005 source
- Partly supportedcites Sallette et al., 2005 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ 2 *-nAChR availability in recently abstinent smokers correlated with the days since last cigarette and the urge to smoke to relieve withdrawal symptoms but not the severity of nicotine dependence, severity of nicotine withdrawal, or the desire to smoke.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
- Rests on an assumption: Urinary cotinine levels below 250 ng/ml indicate sufficient abstinence from smoking.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In smokers, [ 123 I]5-IA uptake was significantly higher throughout the cerebral cortex (26 -36%) and in the striatum (27%) than in nonsmokers, suggesting higher  2 *-nAChR in recently abstinent smokers.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Abstract
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
- Rests on an assumption: Urinary cotinine levels below 250 ng/ml indicate sufficient abstinence from smoking.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“also provided the first evidence that clearance of nicotine or a pharmacologically active metabolite (a metabolite that is occupying the receptor and blocking the radioligand from binding) takes several days after the last administration to clear brain.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The nonhuman primate findings on nicotine-induced β2*-nAChR upregulation and clearance generalize to human smokers.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Voxel-based analyses (df ϭ 30) demonstrated significantly higher  2 *-nAChR availability for a large cluster (T ϭ 5.20; p ϭ 0.000 corrected) that included the parietal cortex [Brodmann's area 40 (BA 40)], cingulate gyrus (BA 31), middle temporal gyrus (BA 39), and for two smaller clusters in the middle frontal gyrus that included BA 6 (T ϭ 4.43; p ϭ 0.03 corrected) and BA 9 (T ϭ 4.19; p ϭ 0.04”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
- Rests on an assumption: Urinary cotinine levels below 250 ng/ml indicate sufficient abstinence from smoking.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ 2 *-nAChR availability in recently abstinent smokers correlated with the days since last cigarette and the urge to smoke to relieve withdrawal symptoms but not the severity of nicotine dependence, severity of nicotine withdrawal, or the desire to smoke.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
- Rests on an assumption: Urinary cotinine levels below 250 ng/ml indicate sufficient abstinence from smoking.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Average regional [ 123 I]5-IA binding decreased from baseline (41-65% change) after 1-2 d withdrawal”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- The authors state this as an assumption: V_T' is proportional to binding potential (Bmax/KD), assuming no change in affinity (KD) and that nondisplaceable uptake does not differ between animals and studies.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The voxel-based analyses demonstrated that  2 *-nAChR availability in the ante- rior cingulate cortex and frontal cortex (BA 5 and BA 6) correlated significantly with the number of days since last cigarette, suggesting that  2 *-nAChR availability increased progressively with continued days of abstinence.”
- Also stated in: § Discussion · plain
“Days since last cigarette Anterior cingulate 14,12,24 405 8.62 0.95 0.004 0.020”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The [123I]5-IA VT' measure reflects β2*-nAChR availability (density of binding sites) in human brain without confounding by differences in blood flow or radioligand delivery.
- Also stated in: § Discussion · plain
- It may state two separate claims as one. 14
- Probably not a substantial claim. 13
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Greater  2 *- nAChR availability is not associated with changes in  2 *-nAChR mRNA (Marks et al., 1992;Peng et al., 1994;Zhang et al., 1994) protein synthesis (Buisson and Bertrand, 2001), rate of receptor internalization, postendocytic trafficking, or lysosomal degradation (Darsow et al., 2005)”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Supportedcites Marks et al., 1992 source
The Marks et al. citation is attached to the mRNA clause, not the later claims about protein synthesis or receptor trafficking. The Discussion reports that chronic nicotine treatment increased high-affinity nicotine binding in mouse brain without changing mRNA for the β subunit likely present in those receptors; it treats the receptor-subunit identification as an inference. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites Peng et al., 1994 source
- Not checked — no full text of the sourcecites Zhang et al., 1994 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The concentration of unmetabolized [ 123 I]5-IA and the percentage of [ 123 I]5-IA not bound to plasma proteins ( f 1 ) did not vary significantly between nonsmokers and smokers [0.31 Ϯ 0.09 and 0.26 Ϯ 0.08 kBq/ml, respectively; 95% confidence interval (Ϫ0.114, 0.009); p ϭ 0.09; and 35.4 Ϯ 3.2 and 36.6 Ϯ 4.9%, respectively; p ϭ 0.44].”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Results
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no significant correlations between regional  2 *-nAChR availability and number of cigarettes smoked per day, severity of nicotine dependence, severity of nicotine withdrawal, or the urge to smoke for either region of interest analyses or voxel-based analyses.”
- Also stated in: § Discussion · plain
“We did not observe a relationship between  2 *-nAChR avail- ability in brain and the number of cigarettes smoked per day”
- Also stated in: § Discussion · plain
“there was no evidence for a significant correlation between  2 *-nAChR avail- ability and the severity of nicotine withdrawal assessed by the MWS on the scan day.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Results
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The [123I]5-IA VT' measure reflects β2*-nAChR availability (density of binding sites) in human brain without confounding by differences in blood flow or radioligand delivery.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This report provides the first direct evidence that brain  2 *-nAChR densities are higher in the striatum, cerebellum, and cerebral cortex during early abstinence in living human smokers compared with nonsmokers”
- Also stated in: § Discussion · plain
“striatal, cortical, and cerebellar [ 123 I]5-IA uptake values were significantly higher in the smokers compared with the nonsmokers ( p values ϭ 0.0002, 0.0001, and 0.0013, respectively), whereas there was no significant difference in thalamic [ 123 I]5-IA uptake.”
- Also stated in: § Discussion · plain
“recently abstinent smokers have more cortical, striatal, and cerebellar  2 *-nAChR sites available for binding than nonsmok- ers”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The [123I]5-IA VT' measure reflects β2*-nAChR availability (density of binding sites) in human brain without confounding by differences in blood flow or radioligand delivery.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were notable regional differences in  2 *-nAChR avail- ability in smokers with robustly higher levels throughout the cerebral cortex, striatum, and cerebellum but not thalamus compared with the nicotine-treated nonhuman primates, which exhibited higher [ 123 I]5-IA binding throughout all brain regions.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The nonhuman primate findings on nicotine-induced β2*-nAChR upregulation and clearance generalize to human smokers.
- Rests on an assumption: The [123I]5-IA VT' measure reflects β2*-nAChR availability (density of binding sites) in human brain without confounding by differences in blood flow or radioligand delivery.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Note the reproducibility of measurement indicated by lack of change between B1 and B2, the profound decrease followed by 1-2 d of withdrawal (41-65% change at 6 weeks of nicotine treatment), and the dramatic increase followed by 7 d of withdrawal (Ͼ200% after 8 weeks of nicotine treatment).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The nonhuman primate findings on nicotine-induced β2*-nAChR upregulation and clearance generalize to human smokers.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Self-reports of menstrual cycle phase were validated by plasma estrogen and progesterone levels.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > [ 123 I]5-IA SPECT imaging of nonhuman primates.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Regional  2 *-nAChR availability was determined by V T Ј (regional activity/total plasma parent), a highly reproducible outcome measure (Staley et al., 2005).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > [ 123 I]5-IA SPECT imaging of nonhuman primates.
What the sources say
- Not checked — no full text of the sourcecites Staley et al., 2005
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Rests on an assumption: V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Although a species difference cannot be ruled out, this divergence may suggest that the ability of nicotine to regulate  2 *-nAChR availability is age or sex dependent because the nonhuman primates were male adolescents and the smokers were male and female adults (Slotkin, 2002;Nguyen et al., 2003).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: The nonhuman primate findings on nicotine-induced β2*-nAChR upregulation and clearance generalize to human smokers.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“animals exposed to nicotine chronically exhibit increased levels of nAChRs in the brain (Marks et al., 1983(Marks et al., , 1985(Marks et al., , 1992;;Schwartz and Kellar, 1983)”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“The interclass coefficient to assess inter-rater reliability (Rousson et al., 2002) ranged between 0.82 and 0.97 for the V T Ј measure across the eight brain regions.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > [ 123 I]5-IA SPECT imaging of nonhuman primates.
What the sources say
- Not checked — no full text of the sourcecites Rousson et al., 2002 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Abstinence was confirmed by daily assessments of urinary cotinine and expired carbon monoxide levels.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Rests on an assumption: Urinary cotinine levels below 250 ng/ml indicate sufficient abstinence from smoking.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Postmortem studies of human brain have suggested that numbers of nAChRs are higher in smokers than in nonsmokers or former smokers (Benwell et al., 1988;Breese et al., 1997;Perry et al., 1999)”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“On the SPECT scan day, urinary cotinine levels were Ͻ250 ng/ml for 14 of 16 smokers and Ͻ1000 ng/ml for two smokers.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Results
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Urinary cotinine levels below 250 ng/ml indicate sufficient abstinence from smoking.
In the paper
“The relationship between greater  2 *-nAChR availability and nAChR function may vary in a region-dependent manner attributable to different subunit combinations that demonstrate increased agonist binding but differ in the effects on function (Rush et al., 2002).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Not checked — no full text of the sourcecites Rush et al., 2002 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Although most withdrawal symptoms resolve after a few days of abstinence, craving (i.e., the urge to smoke) is a prominent feature of nicotine dependence (Tiffany and Drobes, 1991) and is a primary factor associated with relapse (Killen et al., 1997).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Not checked — no full text of the sourcecites Tiffany and Drobes, 1991 source
- Not matchedcites Killen et al., 1997
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The rapid pharmacokinetics were observed, however, after a single administration of a trace dose of intravenous nicotine, and the accumulation of nicotine and/or metabolites (Vainio and Tuominen, 2001) in brain may differ with protracted and repeated nicotine administration.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Not checked — no full text of the sourcecites Vainio and Tuominen, 2001 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Urinary cotinine, the primary metabolite of nicotine, has a longer half-life than nicotine and appears to be a useful indicator of the clearance of nicotine or a metabolite from brain.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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 of the myriad of symptoms and the wide-ranging actions of nicotine on brain neurochemistry, the severity of nicotine withdrawal is likely determined by the complex interplay between  2 *-nAChRs and other neurochemi- cal systems.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Rests on an assumption: The [123I]5-IA VT' measure reflects β2*-nAChR availability (density of binding sites) in human brain without confounding by differences in blood flow or radioligand delivery.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Nicotine is highly lipophilic and, when radiolabeled, demonstrates very high levels of nonspecific brain uptake (Broussolle et al., 1989;Muzic et al., 1998).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Not checked — no full text of the sourcecites Broussolle et al., 1989 source
- Not checked — no full text of the sourcecites Muzic et al., 1998
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Interindividual variability in nicotine metabolism in human smokers is expected because individuals with different CYP2A6 genotypes differentially metabolize nicotine (Tyndale and Sellers, 2001).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Not checked — no full text of the sourcecites Tyndale and Sellers, 2001
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Although  2 subunits exist in several different combi- nations with ␣ 2 , ␣ 3 , ␣ 4 , and ␣ 6 subunits, the ␣ 4  2 combination is most prevalent and also the most sensitive to upregulation by nicotine (Nguyen et al., 2003;Sallette et al., 2004).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Importantly, large individual differences in urinary cotinine clearance have been observed in human smokers over the first week of abstinence, with cotinine levels declining to levels comparable with those in nonsmokers over a 4 -7 d period after smoking cessation.”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The apparent long residence time of nicotine on  2 *-nAChR in brain is sur- prising given that the terminal half-life of nicotine is 1.6 h in macaques (Schoedel et al., 2003) and that radiolabeled nicotine rapidly clears from brain (Crooks and Dwoskin, 1997;Crooks et al., 1997).”
§ Neurobiology of Disease Human Tobacco Smokers in Early Abstinence Have Higher Levels of  2 *Nicotinic Acetylcholine Receptors than Nonsmokers > Discussion
What the sources say
- Not checked — no full text of the sourcecites Schoedel et al., 2003 source
- Not matchedcites Crooks and Dwoskin, 1997
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Crooks et al., 1997
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Nicotine initiates its actions in the brain through nicotinic acetylcholine receptors (nAChRs).
“Nicotine, the addictive chemical in tobacco smoke, initiates its actions in brain through nicotinic acetylcholine receptors (nAChRs).”
The paper relies on this without support.
The addictive properties of tobacco smoke are attributed primarily to nicotine.
“Although tobacco smoke contains Ͼ4000 chemicals, its addictive properties have been attributed primarily to nicotine.”
The authors state this as an assumption.
V_T' is proportional to binding potential (Bmax/KD), assuming no change in affinity (KD) and that nondisplaceable uptake does not differ between animals and studies.
“The primary outcome measure for regional brain uptake was V T Ј, which is proportional to the binding potential (BP) (B max /K D ), assuming that there is no change in affinity (K D ) and that nondisplaceable uptake does not differ between animals and studies.”
The paper relies on this without support.
The time course of nicotine clearance and receptor availability in nonhuman primates is similar enough to humans to determine the necessary abstinence interval for human smokers.
“First, using nonhuman primates treated chronically with nicotine, we estimated the time interval necessary for smokers to abstain from smoking so that residual nicotine would not interfere with [ 123 I]5-IA binding to the  2 *-nAChR as ϳ7 d.”
The paper relies on this without support.
V_T' in humans reflects β2*-nAChR availability without changes in affinity or nondisplaceable uptake.
“Regional  2 *-nAChR availability was determined by V T Ј (regional activity/total plasma parent), a highly reproducible outcome measure (Staley et al., 2005).”
The paper relies on this without support.
Urinary cotinine levels below 250 ng/ml indicate sufficient abstinence from smoking.
“On the SPECT scan day, urinary cotinine levels were Ͻ250 ng/ml for 14 of 16 smokers and Ͻ1000 ng/ml for two smokers.”
The paper relies on this without support.
The nonhuman primate findings on nicotine-induced β2*-nAChR upregulation and clearance generalize to human smokers.
“These findings were substantiated by our experiment in nonhuman primates that confirmed that higher  2 *-nAChR availability is at- tributable to nicotine (vs other chemicals in tobacco smoke)”
The paper relies on this without support.
The [123I]5-IA VT' measure reflects β2*-nAChR availability (density of binding sites) in human brain without confounding by differences in blood flow or radioligand delivery.
“Higher brain [ 123 I]5-IA uptake in recently abstinent smokers suggests greater availability of nicotine binding sites on  2 *- nAChRs.”
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
“In summary, our data extend the findings of previous studies8, 18 which showed that the upregulation of the β2*-nAChR in recently abstinent tobacco smokers was temporary and could be measured with [123I]5-IA SPECT imaging.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“it was found that chronic smokers have more cortical, striatal, and cerebellar β2* nAChRs than non-smokers (Staley et al. 2006).”
From Nicotine Withdrawal (2015) · cites this paper as Staley et al. 2006
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“β2*-nicotinic acetylcholine receptor (β2*-nAChR) availability is higher in recently abstinent smokers compared to never smokers.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“The difference between recently abstinent smokers and never smokers in the previous study8 was of a greater magnitude, e.g., 26-36% in the cerebral cortex and 27% in the striatum, than in the current study, e.g., 21-29% in the cerebral cortex and 22% in the striatum.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“We previously found a negative correlation between the urge to smoke to relieve withdrawal symptoms and β2*-nAChR availability in the sensorimotor cortex at approximately 1 week of abstinence8.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Consistent with our previous study8 we report significantly higher β2*-nAChR availability in smokers at one week of abstinence in the cortex, striatum and cerebellum, but not thalamus compared to nonsmokers.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“This study and previous in vivo PET78 and SPECT8, 18 studies report no upregulation of thalamic β2*-nAChR availability during acute abstinence, which conflicts with postmortem2 and animal8, 79 studies.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“this hypothesis suggests that the increased depressive symptoms observed in some patients following acute cessation from smoking might be explained by the fact that the clearance of nicotine following smoking cessation coupled with persistent nAChR upregulation (Staley et al., 2006) results in increased ability of ACh to activate these upregulated nAChRs.”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Staley et al., 2006
The cited source says what the claim attributes to it.
In the citing paper
“and might impact the ability to maintain abstinence in the clinical population (Staley et al. 2006).”
From Nicotine Withdrawal (2015) · cites this paper as Staley et al. 2006
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, β2* nAChRs in the anterior cingulate and frontal cortex were significantly correlated with the number of days following cessation of smoking.”
From Nicotine Withdrawal (2015) · cites this paper as Staley et al. 2006
The cited source says what the claim attributes to it.
In the citing paper
“Additionally, studies have demonstrated that upregulation of nAChR expression can persist for several days following termination of chronic nicotine (Pietila et al. 1998; Staley et al. 2006).”
From Nicotine Withdrawal (2015) · cites this paper as Staley et al. 2006
The cited source says what the claim attributes to it.
In the citing paper
“In addition, a significant negative correlation was observed between β2* nAChR availability in the post-central gyrus or somatosensory cortex and the urge to relieve withdrawal symptoms by smoking (Staley et al. 2006).”
From Nicotine Withdrawal (2015) · cites this paper as Staley et al. 2006
In the citing paper
“Increased nAChRs are also seen with in vivo imaging techniques in baboon brain after chronic administration of nicotine (Kassiou et al., 2001) and the brains of current smokers (Staley et al., 2006;Wu ¨llner et al., 2008).”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Staley et al., 2006
In the citing paper
“In chronic smokers, abstinence from nicotine increases the availability of unbound α4β2 nAChRs, which in turn contributes to abstinence symptoms (35).”
From Varenicline improves mood and cognition during smoking abstinence (2009) · cites this paper as [35]
In the citing paper
“Abstinent smokers compared to nonsmokers had higher levels of β2* nAChRs, which returned to baseline between 3-12 weeks, and elevated nAChR levels correlated with urge to smoke (Cosgrove et al., 2009; Mamede et al., 2007; Staley et al., 2006).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Staley et al., 2006
In the citing paper
“Abstinent smokers compared to nonsmokers had higher levels of β2* nAChRs, which returned to baseline between 3-12 weeks, and elevated nAChR levels correlated with urge to smoke (Cosgrove et al., 2009; Mamede et al., 2007; Staley et al., 2006).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Staley et al., 2006
In the citing paper
“results from studies of abstinent smokers showing a relationship between β2* nAChR concentration and cravings to smoke to reduce withdrawal symptoms (Staley et al., 2006).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Staley et al., 2006
In the citing paper
“Nicotine-induced “up-regulation” has been replicated many times in systems ranging from clonal cell lines to primary neurons in culture, to mouse models, and to smokers’ brains (Breese et al., 1997; Court et al., 1998; Staley et al., 2006; Mukhin et al., 2008; Albuquerque et al., 2009; Lester et al., 2009).”
From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Staley et al., 2006
In the citing paper
“Human smokers also show increased levels of nAChRs in functional magnetic resonance imaging and post mortem measurements (6–9).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [9]
In the citing paper
“Imaging studies of nicotine abuse report upregulation of the nicotinic receptor (Cosgrove et al., 2009; Mukhin et al., 2008; Staley et al., 2006; Wullner et al., 2008)”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Staley et al., 2006
In the citing paper
“The magnitude of the differences in VT/fP between smokers and nonsmokers was similar to that found in a recent SPECT study (28).”
From Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380 (2008) · cites this paper as [28]
In the citing paper
“That the percentage differences in VT/fP measured with 2FA at 2 d after the last smoked cigarette are similar to those assayed with 5IA at approximately 7 d after the last cigarette suggests that the receptor density in the smokers has already started to decline at 7 d.”
From Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380 (2008) · cites this paper as [28]
In the citing paper
“Taken together, results from 2 published SPECT studies (28,30) and the current PET study suggest that the greater receptor density in smokers declines over the first 3 wk after smoking cessation and approaches the level observed in nonsmokers.”
From Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380 (2008) · cites this paper as [28]
In the citing paper
“In that study and in the present PET study, almost no difference in VT/fP in the thalamus was demonstrated.”
From Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380 (2008) · cites this paper as [28]
In the citing paper
“As mentioned, the observed changes in VT/fP were similar to those observed with SPECT and 5IA as the radioligand (28). This similarity was somewhat unexpected.”
From Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380 (2008) · cites this paper as [28]
In the citing paper
“Previous studies suggest that the upregulated pool of nAChRs arising from long-term exposure to nicotine may drive elements of the nicotine withdrawal syndrome (Turner et al., 2011;Gould et al., 2012), and this protracted upregulation of nAChRs has been correlated with reduced ability to maintain abstinence in the clinical population (Staley et al., 2006).”
From Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors (2014) · cites this paper as Staley et al., 2006
Citations
Cites
The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire
HEATHERTON, T. F., KOZLOWSKI, L. T., FRECKER, R. C., & FAGERSTROM, K. (1991) · British Journal of Addiction · doi:10.1111/j.1360-0443.1991.tb01879.x · Cited by 10,738 · cited 5×
“The severity of nicotine dependence was assessed using the Fagerström Test for Nicotine Dependence (FTND) (Heatherton et al., 1991), nicotine withdrawal symptoms were assessed using the Minnesota Withdrawal Questionnaire (MWQ) (Hatsukami et al., 1984), and the urge to smoke (or craving) was assessed using the Urge to…”
MethodInfluentialSigns and Symptoms of Tobacco Withdrawal
Hughes, J. R. (1986) · Archives of General Psychiatry · doi:10.1001/archpsyc.1986.01800030107013 · Cited by 1,669 · cited 1×
“Because the 2*-nAChR is the initial site of action of nicotine, adaptive changes during acute abstinence may be associated with nicotine withdrawal symptoms that emerge within hours after the last cigarette and persist for 3– 4 weeks (Hughes and Hatsukami, 1986).”
BackgroundPicciotto, M. R., Zoli, M., Rimondini, R., Léna, C., Marubio, L. M., Pich, E. M., Fuxe, K., & Changeux, J.-P. (1998) · Nature · doi:10.1038/34413 · Cited by 1,320 · cited 2×
“Because the reinforcing properties of nicotine have been linked specifically to nAChRs that contain the 2 subunit ( 2*-nAChRs) (Picciotto et al., 1998), an understanding of the adaptive changes in 2*-nAChR number during acute abstinence and their relationship to behavioral correlates of tobacco…”
BackgroundSelf-citationGrant, B. F., Hasin, D. S., Chou, S. P., Stinson, F. S., & Dawson, D. A. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.11.1107 · Cited by 1,262 · cited 1×
“Despite the well known health risks of tobacco smoking, 24.9% of the United States population continues to smoke (Grant et al., 2004).”
BackgroundInfluentialThe development and initial validation of a questionnaire on smoking urges
TIFFANY, S. T., & DROBES, D. J. (1991) · British Journal of Addiction · doi:10.1111/j.1360-0443.1991.tb01732.x · Cited by 974 · cited 3×
“Although most withdrawal symptoms resolve after a few days of abstinence, craving (i.e., the urge to smoke) is a prominent feature of nicotine dependence (Tiffany and Drobes, 1991) and is a primary factor associated with relapse (Killen et al., 1997).”
BackgroundMethodMolecular and cellular aspects of nicotine abuse
Dani, J. A., & Heinemann, S. (1996) · Neuron · doi:10.1016/s0896-6273(00)80112-9 · Cited by 605
Evidence that Tobacco Smoking Increases the Density of (−)‐[3H]Nicotine Binding Sites in Human Brain
Benwell, M. E. M., Balfour, D. J. K., & Anderson, J. M. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb10600.x · Cited by 551 · cited 1×
“Postmortem studies of human brain have suggested that numbers of nAChRs are higher in smokers than in nonsmokers or former smokers (Benwell et al., 1988; Breese et al., 1997; Perry et al., 1999), and animals exposed to nicotine chronically exhibit increased levels of nAChRs in the brain (Marks et…”
BackgroundNicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment
Marks, M., Pauly, Jr., Gross, S., Deneris, E., Hermans-Borgmeyer, I., Heinemann, S., & Collins, A. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02765.1992 · Cited by 551 · cited 3×
“Greater 2*nAChR availability is not associated with changes in 2*-nAChR mRNA (Marks et al., 1992; Peng et al., 1994; Zhang et al., 1994) protein synthesis (Buisson and Bertrand, 2001), rate of receptor internalization, postendocytic trafficking, or lysosomal degradation (Darsow et al.”
BackgroundNicotinic Cholinergic Receptor Binding Sites in the Brain: Regulation in Vivo
Schwartz, R. D., & Kellar, K. J. (1983) · Science · doi:10.1126/science.6828889 · Cited by 479 · cited 1×
“…that numbers of nAChRs are higher in smokers than in nonsmokers or former smokers (Benwell et al., 1988; Breese et al., 1997; Perry et al., 1999), and animals exposed to nicotine chronically exhibit increased levels of nAChRs in the brain (Marks et al., 1983, 1985, 1992; Schwartz and Kellar, 1983).”
BackgroundEffects of chronic nicotine infusion on tolerance development and nicotinic receptors
Marks, M. J., Burch, J. B., & Collins, A. C. (1983) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21831-6 · Cited by 464 · cited 1×
“…that numbers of nAChRs are higher in smokers than in nonsmokers or former smokers (Benwell et al., 1988; Breese et al., 1997; Perry et al., 1999), and animals exposed to nicotine chronically exhibit increased levels of nAChRs in the brain (Marks et al., 1983, 1985, 1992; Schwartz and Kellar, 1983).”
Background
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Items 101–200 of 223
Evaluation of 18F-nifene binding to α4β2 nicotinic receptors in the rat brain using microPET imaging
Kant, R., Constantinescu, C. C., Parekh, P. K., Pandey, S. K., Pan, M., Easwaramoorthy, B., & Mukherjee, J. (2011) · EJNMMI Research · doi:10.1186/2191-219x-1-6 · Cited by 26
“Human imaging studies, using SPECT imaging agent 5-(123)Iiodo-A-85380 and PET imaging agent 2-(18)F-fluoro-A85380, have also identified an increase in receptor density among smokers versus nonsmokers, suggesting 2(18)F-fluoro-A-85380 to be a reliable PET method for further tobacco studies [12,13].”
Cole, R. D., Poole, R. L., Guzman, D. M., Gould, T. J., & Parikh, V. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3754-4 · Cited by 25
“Moreover, human postmortem studies have also shown higher densities of α4β2 nAChRs in the cortex and striatum of smokers (Perry et al. 1999; Staley et al. 2006).”
Brain activity and emotional processing in smokers treated with varenicline
Loughead, J., Ray, R., Wileyto, E. P., Ruparel, K., O'Donnell, G. P., Senecal, N., Siegel, S. J., Gur, R. C., & Lerman, C. E. (2011) · Addiction Biology · doi:10.1111/j.1369-1600.2011.00324.x · Cited by 24
“In abstinent smokers, the availability of unbound a4b2 nAChRs is associated with urges to smoke (Staley et al. 2006).”
BackgroundMcClernon, F. J. (2009) · Journal of Dual Diagnosis · doi:10.1080/15504260902869204 · Cited by 25
“…photon emission computed tomography (SPECT; a method similar to PET) show that smokers have higher densities of α4β2 nicotinic receptors both in cerebral cortex and in striatum (Staley et al., 2006). α4β2 receptor up-regulation in smokers was recently confirmed in a PET study (Mukhin et al., 2008).”
12 h abstinence-induced right anterior insula network pattern changes in young smokers
Bi, Y., Zhang, Y., Li, Y., Yu, D., Yuan, K., & Tian, J. (2017) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2017.02.019 · Cited by 23
DeDominicis, K. E., Sahibzada, N., Olson, T. T., Xiao, Y., Wolfe, B. B., Kellar, K. J., & Yasuda, R. P. (2017) · Molecular Pharmacology · doi:10.1124/mol.116.106880 · Cited by 24
Hussmann, G. P., DeDominicis, K. E., Turner, J. R., Yasuda, R. P., Klehm, J., Forcelli, P. A., Xiao, Y., Richardson, J. R., Sahibzada, N., Wolfe, B. B., et al. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12653 · Cited by 23
“, 1999), as well as in brain imaging studies of current smokers (Staley et al., 2006; Wüllner et al., 2008; Cosgrove et al., 2009).”
Brašić, J. R., Zhou, Y., Musachio, J. L., Hilton, J., Fan, H. S., Crabb, A. H., Endres, C. J., Reinhardt, M. J., DOĞAN, A. S., Alexander, M., et al. (2009) · Synapse · doi:10.1002/syn.20611 · Cited by 23
“People apparently must abstain from nicotine for at least 7 days to estimate the density of unoccupied nicotinic receptors without the effect of residual nicotine (Staley et al., 2006).”
BackgroundNitta, H., Kinoyama, M., Watanabe, A., et al. (2007) · Clinical and Experimental Medicine · doi:10.1007/s10238-007-0144-y · Cited by 23
“The molecular physiological bases in the brain for the difficulties involved in giving up smoking have recently become clear [7], and especially the difficulties in smokers of cigarettes containing menthol (70% of Afro-Americans) have been pointed out [8].”
BackgroundSelegiline Transdermal System (STS) as an Aid for Smoking Cessation
Kahn, R., Gorgon, L., Jones, K. M., McSherry, F., Glover, E. D., Anthenelli, R. M., Jackson, T., Williams, J. M., Murtaugh, C., Montoya, I. D., et al. (2011) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntr143 · Cited by 23
Neural correlates of 12-h abstinence-induced craving in young adult smokers: a resting-state study
Li, Y., Yuan, K., Bi, Y., Guan, Y., Cheng, J., Zhang, Y., Shi, S., Lu, X., Yu, D., & Tian, J. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-016-9544-3 · Cited by 23
Alasmari, F. F., Alexander, L. E. C., Drummond, C. A., & Sari, Y. (2018) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2018.02.031 · Cited by 23
“These data are consistent with previous studies reporting similar effects of tobacco smoke in humans (Staley et al., 2006; Garlichs et al., 2009; Herr et al., 2009; Knackstedt et al., 2009).”
ResultMultidimensional Intersection of Nicotine, Gene Expression, and Behavior
Sherafat, Y., Bautista, M. R., & Fowler, C. D. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.649129 · Cited by 25
“Data derived from animal models provides further evidence of increased nicotine-mediated expression for a subset of nAChR subunits in a region-specific manner (Marks et al., 1987, 1992; Adriani et al., 2003; Staley et al., 2006; Nashmi et al., 2007).”
BackgroundTranslational NeuroImaging of the CNS: Novel Pathways to Drug Development
Fox, G. B., Chin, C.-L., Luo, F. R., Day, M., & Cox, B. F. (2009) · Molecular Interventions · doi:10.1124/mi.9.6.6 · Cited by 22
Esterlis, I., Cosgrove, K., Batis, J. C., Bois, F., Kloczynski, T., Stiklus, S. M., Perry, E. B., Tamagnan, G. D., Seibyl, J. P., Makuch, R., et al. (2009) · Synapse · doi:10.1002/syn.20688 · Cited by 24
“In recently abstinent tobacco smokers (4–7 days), nAChR numbers are higher (Staley et al., 2006), whereas cortical GABA levels are lower in recently abstinent women smokers (2 days) compared to nonsmokers (Epperson et al., 2005).”
BackgroundMethodInfluentialSelf-citationVossel, S., Warbrick, T., Mobascher, A., Winterer, G., & Fink, G. R. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881110391830 · Cited by 19
“At the receptor level, in vitro studies have shown that nicotinic acetylcholine receptors in the brain (in particular a2b4 and a7 subtypes) are increased and upregulated in response to chronic nicotine exposure or chronic smoking (Buisson and Bertrand, 2002; Perry et al., 1999; Staley et al., 2006).”
BackgroundEsterlis, I., McKee, S. A., Kirk, K., Lee, D. S., Bois, F., Stiklus, S. M., Seibyl, J. P., Krishnan‐Sarin, S., O’Malley, S. S., Staley, J. K., et al. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2011.00403.x · Cited by 21
“Cotinine levels were measured in plasma as described previously (Staley et al. 2006; Esterlis et al. 2009).”
MethodSelf-citationBrody, A. L., Hubert, R., Mamoun, M. S., Enoki, R., Garcia, L. Y., Abraham, P., Young, P., & Mandelkern, M. A. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4367-x · Cited by 21
“Cigarette smoking”
BackgroundOgawa, M., Tsukada, H., Hatano, K., Ouchi, Y., Saji, H., & Magata, Y. (2009) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.32.337 · Cited by 21
Review: Nicotinic receptors and stages of nicotine dependence
Brennan, K., Lea, R. A., Fitzmaurice, P. S., & Truman, P. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108100256 · Cited by 22
Govind, A. P., Vallejo, Y. F., Stolz, J. R., Yan, J.-Z., Swanson, G. T., & Green, W. N. (2017) · eLife · doi:10.7554/elife.25651 · Cited by 17
“Recent studies using PET imaging in humans found that reversal of a4b2R upregulation was correlated with less smoking relapse (Brody et al., 2013; Staley et al., 2006; Cosgrove et al., 2009).”
BackgroundMouse model predicts effects of smoking and varenicline on event-related potentials in humans
Rudnick, N. D., Strasser, A. A., Phillips, J. M., Jepson, C., Patterson, F., Frey, J. M., Turetsky, B. I., Lerman, C. E., & Siegel, S. J. (2010) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntq049 · Cited by 17
“, a4b2 nAChRs) in humans and nonhuman primates (Staley et al., 2006).”
BackgroundSex differences in tobacco smokers: Executive control network and frontostriatal connectivity
McCarthy, J. M., Dumais, K. M., Zegel, M., Pizzagalli, D. A., Olson, D. P., Moran, L. V., & Janes, A. C. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2018.11.023 · Cited by 18
Stoker, A. K., Marks, M. J., & Markou, A. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.05.062 · Cited by 16
“Specifically, in humans, the early stages of smoking cessation were characterized by increased levels of β2* nACh receptors (Staley et al., 2006).”
BackgroundBrain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler
Esterlis, I., Mitsis, E. M., Batis, J. C., Bois, F., Picciotto, M. R., Stiklus, S. M., Kloczynski, T., Perry, E. B., Seibyl, J. P., McKee, S. A., et al. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710001227 · Cited by 17
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“Related studies using iodide 123-labelled 5iodo-A-85380 ([(123)I]5-IA; herein referred to as 5IA) SPECT imaging provided evidence that smokers have increased levels of a4b2* nAChRs in thalamic, striatal and cortical brain regions at 1 week but not 24 h into withdrawal relative to non-smokers.(26,79) Notably,”
MethodMcClure‐Begley, T. D., Esterlis, I., Stone, K. L., Lam, T. T., Grady, S. R., Colangelo, C. M., Lindstrom, J. M., Marks, M. J., & Picciotto, M. R. (2016) · eNeuro · doi:10.1523/eneuro.0166-16.2016 · Cited by 16
Self-citationBiotechnology and the Treatment of Addictive Disorders
Elkashef, A. M., Biswas, J., Acri, J. B., & Vocci, F. J. (2007) · BioDrugs · doi:10.2165/00063030-200721040-00006 · Cited by 16
“These molecular differences are extremely im- chronic exposure to nicotine and would explain some of the portant in targeting and developing pharmacologic tools to treat neuroadaptive processes involved with smoking.[19] these two addictions, although some of the neuroadaptations pro- In summary, multiple factors play…”
BackgroundMetaxas, A., Al‐Hasani, R., Farshim, P. P., Tubby, K. C., Berwick, A., Ledent, C. A., Hourani, S. M. O., Kitchen, I., & Bailey, A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.023 · Cited by 15
Kirsch, G. E., Fedorov, N. B., Kuryshev, Y. A., Liu, Z., Armstrong, L. C., & Orr, M. S. (2016) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.688 · Cited by 14
Multimodal Neuroimaging Differences in Nicotine Abstinent Smokers Versus Satiated Smokers
Chaarani, B., Spechler, P. A., Ivanciu, A., Snowe, M. P., Nickerson, J. P., Higgins, S. T., & Garavan, H. (2018) · Nicotine & Tobacco Research · doi:10.1093/ntr/nty070 · Cited by 15
Cosgrove, K., Kloczynski, T., Bois, F., Pittman, B. P., Tamagnan, G. D., Seibyl, J. P., Krystal, J. H., & Staley, J. K. (2010) · Synapse · doi:10.1002/syn.20795 · Cited by 15
“This paradigm has demonstrated high test-retest reliability in rhesus monkeys (Staley et al., 2006).”
BackgroundMethodSelf-citationSemenova, S., Jin, X., McClure‐Begley, T. D., Tadman, M. P., Marks, M. J., & Markou, A. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2018.06.002 · Cited by 13
“did not correlate with the severity of nicotine withdrawal assessed with the Minnesota Withdrawal Questionnaire (Staley et al., 2006).”
BackgroundMethodSPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals
Esterlis, I., Cosgrove, K., Petrakis, I. L., McKee, S. A., Bois, F., Krantzler, E., Stiklus, S. M., Perry, E. B., Tamagnan, G. D., Seibyl, J. P., et al. (2010) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.12.006 · Cited by 14
Self-citationEffects of nicotine and stress exposure across generations in C57BL/6 mice
Yohn, N. L., Caruso, M. J., & Blendy, J. A. (2019) · Stress · doi:10.1080/10253890.2018.1532991 · Cited by 13
“In addition, this dose upregulates nicotinic acetylcholine receptors in the brain of rodents (Yohn, Turner, & Blendy, 2014), a hallmark of chronic NIC use in humans (Staley, 2006).”
BackgroundGarcia‐Rivas, V., Fiancette, J.-F., Cannella, N., Carbo‐Gas, M., Renault, P., Tostain, J., & Deroche‐Gamonet, V. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00159 · Cited by 12
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Yang, K., McLaughlin, I., Shaw, J. K., Cardé, N. A. Q., Dani, J. A., & Biasi, M. D. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109547 · Cited by 12
Esterlis, I., Hillmer, A. T., Bois, F., Pittman, B. P., McGovern, E. M., O’Malley, S. S., Picciotto, M. R., Yang, B., Gelernter, J. E., & Cosgrove, K. (2016) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntw081 · Cited by 14
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Duncan, P. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139025515.013 · Cited by 12
Smoking modulates language lateralization in a sex-specific way
Hahn, C., Pöğün, Ş., & Güntürkün, O. (2010) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2010.10.014 · Cited by 12
“…the underlying mechanism is still debated (Barik & Wonnacott, 2009), data from both human smokers and animal models demonstrate that nicotine exposure leads to nAChR up-regulation (reviewed in Picciotto et al., 2008) which persists for at least 7 days of smoking abstinence (Staley et al., 2006).”
Poole, R. L., Connor, D. A., & Gould, T. J. (2014) · Behavioral Neuroscience · doi:10.1037/bne0000003 · Cited by 11
Storage, S. S., Mandelkern, M. A., Phuong, J., Kozman, M., Neary, M. K., & Brody, A. L. (2013) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2013.07.010 · Cited by 10
“…given that this study included a rating scale with 4 subscales and 4 ROIs, and because smokers have been consistently shown to have similar nAChR changes in almost all brain regions studied (Staley et al., 2006; Mamede et al., 2007; Mukhin et al., 2008;Wullner et al., 2008; Brody et al., 2013).”
BackgroundLotfipour, S., Mandelkern, M. A., & Brody, A. L. (2011) · Current Medical Imaging Formerly Current Medical Imaging Reviews · doi:10.2174/157340511795445676 · Cited by 9
Foll, B. L., Chefer, S. I., Kimes, A. S., Stein, E. A., Goldberg, S. R., & Mukhin, A. G. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4250-9 · Cited by 9
“Radiochemical purity product was greater than 98 %, and specific activity was in the range from 106 to 648 GBq/μmol (313±166 GBq/μmol, average±SD).”
InfluentialDensity of α4β2* nAChR on the surface of neurons is modulated by chronic antagonist exposure
Zambrano, C. A., Short, C. A., Salamander, R. M., Grady, S. R., & Marks, M. J. (2015) · Pharmacology Research & Perspectives · doi:10.1002/prp2.111 · Cited by 8
“In vivo PET scan studies confirm that smokers have a higher density of nAChR than nonsmokers and the regional differences in the extent of upregulation similar to those seen with animal studies (Staley et al. 2006; Mukhin et al. 2008).”
ResultSmoking and Neuroimaging: A Review
Hedy Kober, A., & DeLeone, C. M. (2011) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-011-0201-5 · Cited by 9
Granulocytes as models for human protein marker identification following nicotine exposure
Mulcahy, M. J., & Lester, H. A. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14010 · Cited by 9
“In the human CNS, β2* nAChRs have been shown to up-regulate in some brain regions of smokers compared to non-smokers (Staley et al. 2006; Brody et al. 2013).”
BackgroundMoretti, M., Fasoli, F., Gotti, C., & Marks, M. J. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13896 · Cited by 8
“, 2011), human tobacco users (Benwell et al., 1988; Breese et al., 1997; Perry et al., 1999; Staley et al., 2006) and cultured cells expressing α4β2*nAChR natively or following transfection (Davila-Garcia et al.”
The incentive amplifying effects of nicotine: Roles in alcohol seeking and consumption
King, C. P., & Meyer, P. (2022) · Advances in pharmacology · doi:10.1016/bs.apha.2021.10.008 · Cited by 10
Luckhaus, C., Henning, U., Ferrea, S., Musso, F., Mobascher, A., & Winterer, G. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0743-1 · Cited by 8
“At baseline culture condition, [(3)H]-nicotine binding on B-lymphoblasts was not statistically different between healthy smokers and never-smokers, which on first sight is not in line with earlier post-mortem, neuroimaging and peripheral leucocyte findings (Breese et al. 2000; Cormier et al. 2004; Staley et al. 2006;…”
ResultGolden, A. K., & Davis, J. M. (2025) · Journal of Multidisciplinary Healthcare · doi:10.2147/jmdh.s509971 · Cited by 10
“28,29 The degree of nAChR upregulation is associated with the severity of withdrawal symptoms and difficulty quitting smoking.”
Calakos, K. C., Hillmer, A. T., Anderson, J. M., LeVasseur, B., Baldassarri, S. R., Angarita, G. A., Matuskey, D., Kapinos, M., Zheng, M., Huang, Y. H., et al. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01535-1 · Cited by 8
“PET imaging also occurred at the optimal timepoint of one week of abstinence: early enough to observe persistent neurobiological adaptations, and late enough to ensure nicotine clearance from the brain [21, 22, 58].”
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Surin, A., Kryukova, E., Strukov, A. S., Zhmak, M. N., Talka, R., Tuominen, R., Salminen, O., Khiroug, L., Kasheverov, I., & Tsetlin, V. (2012) · Russian journal of bioorganic chemistry · doi:10.1134/s1068162012020112 · Cited by 5
Administration of Nicotine Can Inhibit Myopic Growth in Animal Models
Thomson, K., Karouta, C., & Ashby, R. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.11.29 · Cited by 5
Brody, A. L., Mischel, A. K., Sanavi, A. Y., Wong, A., Bahn, J. H., Minassian, A., Morgan, E. E., Rana, B. K., Hoh, C. K., Vera, D. R., et al. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-02035-6 · Cited by 5
“We hypothesized that effects of smoking on the marker for neuroin fl ammation would occur throughout the brain, since prior research by our group [37, 38, 40 – 43] and others [44, 45] demonstrates widespread effects of smoking when studying systems that are widely distributed.”
The Effects of Nicotine on Learning and Memory
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Mecamylamine for Treatment of People With Dual Diagnoses of Depression and Alcohol Dependence
Ralevski, E., Jane, J. S., O’Brien, E. M., Edens, E. L., Arnaout, B., Kerfoot, K. E., Keegan, K. A., Weiner, J., Russo, M., & Petrakis, I. L. (2013) · Journal of Dual Diagnosis · doi:10.1080/15504263.2013.835163 · Cited by 6
“Another explanation for the nAChR role in drinking and mood symptoms is that the nAChRs may exert their rewarding and mood effects by acting on the N-methyl-D-aspartate (NMDA) and GABA receptors (Dani & Harris, 2005; Krystal et al., 2006; Mason et al., 2006; Staley et al., 2006).”
Backgroundα4β2 nicotinic acetylcholine receptors intrinsically influence body weight in mice
Dezfuli, G., Olson, T. T., Martin, L. M., Keum, Y., Siegars, B., Desai, A., Uitz, M., Sahibzada, N., Gillis, R. A., & Kellar, K. J. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107921 · Cited by 5
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Functional Brain Imaging of Tobacco Exposure in Humans
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“[86] 16 smokers; 16 non-smokers SPECT, 5-IA 7 days Compared to non-smokers, recently abstinent smokers had ↑ 5-IA uptake in striatum, parietal cortex, frontal cortex, anterior cingulate, temporal cortex, occipital cortex and cerebellum”
BackgroundInfluentialAbnormalities of Neurotransmission in Drug Addiction
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Human Brain Imaging of Acetylcholine Receptors
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How to Study Smoking and Drinking with PET
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Application of Functional Neuroimaging to Examination of Nicotine Dependence
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Preclinical and Clinical Aspects of Nicotinic Acetylcholine Receptor Imaging
Brust, P., Deuther‐Conrad, W., Donat, C. K., Barthel, H., Riss, P. J., Paterson, L. M., Hoepping, A., Sabri, O., & Cumming, P. D. (2020) · Springer eBooks · doi:10.1007/978-3-030-53176-8_18 · Cited by 5
Visión general de la neurobiología y genética en la adicción a la nicotina
Pérez-Rubio, G., Urdapilleta-Herrera, E. D. C., Camarena, Á., Reséndiz-Hernández, J. M., Guerra, M. M., Venegas, A. R., Sansores, R. H., & Falfán‐Valencia, R. (2011) · NCT Neumología y Cirugía de Tórax · Cited by 2
Biomarkers in Substance Use Disorder
Lane, S. D., Yoon, J. H., Heads, A. M. B., de Dios, C., Yammine, L., Hong, J. H., Webber, H. E., Weaver, M. F., Schmitz, J. M., & Walss‐Bass, C. (2023) · Springer eBooks · doi:10.1007/978-3-031-43356-6_18 · Cited by 1
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“Chronic nicotine exposure leads to desensitization and internalization of α 4 β 2-nAChRs, which triggers compensatory receptor upregulation over time (Staley et al., 2006; Cosgrove et al., 2009).”
Transdisciplinary Tobacco Use Research Centers: Research achievements and future implications
Baker, T. B., Cummings, K. M., Hatsukami, D. K., Johnson, C. A., Lerman, C. E., NIAURA, R. S., & O’Malley, S. S. (2009) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntp112 · Cited by 2
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Nicotine Addiction and Alpha4beta2* Nicotinic Acetylcholine Receptors
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Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons
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Substance Use Disorders: A Biopsychosocial Perspective
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Nicotinic Cholinergic Signaling in the Human Brain – Systems Perspective
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The Relationship Between Mood, Stress, and Tobacco Smoking
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Past Cigarette Smoking Is More Common among Those with Cholinergic Than Noncholinergic Dementias
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No al “hábito”, sí a la “adicción”. Análisis crítico de un eufemismo asociado al tabaco
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NeuralSubstratesofAbstinence-InducedCigaretteCravings inChronicSmokers
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Nicotinic Acetylcholine Receptors in Alzheimer’s and Parkinson’s Disease
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Prenatal nicotine exposure and molecular mechanisms of memory impairment
Parameshwaran, K. (2008)
Molecular imaging of substance abuse
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Emergent Cognitive Impairment During Early Nicotine Withdrawal ∗
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“Increased nAChR expression due to chronic nicotine can last up to 7-21 days after the last nicotine exposure (Marks et al., 1983; Schwartz and Kellar, 1985; Staley et al., 2006; Hilario et al., 2012).”
BackgroundIn Vivo Imaging of Nicotinic Acetylcholine Receptors in the Central Nervous System
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“were the first to noninvasively detect higher levels of α4β2 nAChRs in smokers (Staley et al. 2006).”
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“The clinical implications of such findings suggest that nicotine replacement therapy can be helpful to tolerate the nicotine and alcohol withdrawal symptoms in smokers with alcohol dependency [3,4].”
BackgroundMarks, M. J., Loetz, E. C., Ortiz, N. C., Herder, P., & Collins, A. C. (2020) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000575
“, 1983; Schwartz and Kellar, 1983) and tobacco use in humans (Benwell et al., 1988; Breese et al., 1997; Staley et al., 2006) result in the upregulation of high affinity nicotinic binding sites.”
BackgroundPsychiatric Disorders, Personality, and Developmental Factors
Duncan, P. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781139025515.009
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Use Disorders of Cocaine and Methamphetamine
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Tranquilizers and Sedative Use Disorders
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Metadata
- Authors
- Staley, J. K., Krishnan-Sarin, S., Cosgrove, K. P., Krantzler, E., Frohlich, E., Perry, E., Dubin, J. A., Estok, K., Brenner, E., Baldwin, R. M., Tamagnan, G. D., Seibyl, J. P., Jatlow, P., Picciotto, M. R., London, E. D., O'Malley, S., & van Dyck, C. H.
- Affiliations
- Yale University (US)
- VA Connecticut Healthcare System (US)
- Institute for Neurodegenerative Disorders (US)
- University of California, Los Angeles (US)
- Corresponding author
- Staley, Julie K.
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-08-23
- Volume
- 26
- Issue
- 34
- Pages
- 8707-8714
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674379
- OpenAlex
- W2165081822
- Semantic Scholar
- d596f30a7d3efb87530451c65cfcafb05ddb4f13
- Cited by
- 229
- References
- 64
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 26 · 2019: 7 · 2018: 16 · 2017: 8 · 2016: 13 · 2015: 11 · 2014: 18 · 2013: 20 · 2012: 9
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (P50AA015632, K01AA000288)
- National Institute on Drug Abuse (K02DA000436, R01DA015577, P50DA013334)
- 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
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- nicotine withdrawal, smoking abstinence, nicotine dependence, striatum, cerebral cortex, urinary cotinine, carbon monoxide
- MeSH terms
- Adult, Animals, Azetidines, Cerebral Cortex, Corpus Striatum, Female, Humans, Macaca mulatta, Male, Middle Aged, Pyridines, Receptors, Nicotinic, Smoking, Nicotiana, Tomography, Emission-Computed, Single-Photon, Smoking Cessation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-08 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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