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
Flagged first, then by citations
7 of the 64 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Structural and functional diversity of native brain neuronal nicotinic receptors
Gotti, C., Clementi, F., Fornari, A., Gaimarri, A., Guiducci, S., Manfredi, I., Moretti, M., Pedrazzi, P., Pucci, L., & Zoli, M. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.024 · Cited by 469
“have high β2* receptor levels for at least seven days after stopping smoking [123].”
BackgroundPICCIOTTO, M., ADDY, N., MINEUR, Y., & BRUNZELL, D. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.005 · Cited by 460
“Indeed, 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 abilit…”
BackgroundInfluentialSelf-citationMolecular tracers for the PET and SPECT imaging of disease
Pimlott, S. L., & Sutherland, A. J. (2010) · Chemical Society Reviews · doi:10.1039/b922628c · Cited by 379
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis
Mineur, Y. S., & Picciotto, M. R. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.004 · Cited by 285
Self-citationNeural substrates of abstinence-induced cigarette cravings in chronic smokers
Wang, Z., Faith, M., Patterson, F., Tang, K., Kerrin, K., Wileyto, E. P., Detre, J. A., & Lerman, C. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2966-07.2007 · Cited by 256
Why do patients with schizophrenia smoke?
Winterer, G. (2010) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e3283366643 · Cited by 238
Smoking, quitting, and psychiatric disease: A review
Aubin, H., Rollema, H., Svensson, T. H., & Winterer, G. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.06.007 · Cited by 241
Varenicline improves mood and cognition during smoking abstinence
Patterson, F., Jepson, C., Strasser, A. A., Loughead, J., Perkins, K. A., Gur, R. C., Frey, J. M., Siegel, S., & Lerman, C. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.08.028 · Cited by 222
Smoking, nicotine and neuropsychiatric disorders
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“…in humans have also confirmed both the upregulation of a4b2 receptors after chronic NIC administration (smoking) and the termination of upregulation after approximately 21 days of smoking cessation (Mamede et al., 2007; Staley et al., 2006; Wullner et al., 2008; Kassiou et al., 2001).”
Backgroundα6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson’s Disease
Quik, M., & Wonnacott, S. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003269 · Cited by 201
“Long-term nicotine administration, delivered in multiple forms (injection, minipump, drinking water, or self-administration), increases the numbers of 4 2* binding sites throughout the brain in experimental animal models and humans (Marks et al., 1983; Schwartz and Kellar, 1983; Benwell et al., 1988; Perry et al., 199…”
BackgroundSex Differences in the Brain's Dopamine Signature of Cigarette Smoking
Cosgrove, K. P., Wang, S., Kim, S., McGovern, E., Nabulsi, N., Gao, H., Labaree, D., Tagare, H., Sullivan, J. M., & Morris, E. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3661-14.2014 · Cited by 168
“Overnight abstinence was confirmed with breath CO levels 10 ppm. Plasma nicotine and cotinine levels were measured as previously described (Staley et al., 2006).”
Self-citationSrinivasan, R., Pantoja, R., Moss, F. J., Mackey, E. D. W., Son, C. D., Miwa, J., & Lester, H. A. (2011) · Journal of General Physiology · doi:10.1085/jgp.201010532 · Cited by 169
McLaughlin, I., Dani, J. A., & De Biasi, M. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/978-3-319-13482-6_4 · Cited by 191
“Using a radioligand with specificity for β2containing nAChRs, which enabled the use of single-photon emission computed tomography (SPECT) (Staley et al. 2006), it was found that chronic smokers have more cortical, striatal, and cerebellar β2* nAChRs than non-smokers (Staley et al.”
BackgroundInfluentialImaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity
Trifilieff, P., & Martinez, D. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.031 · Cited by 171
“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) and an imaging study of opiate abusers showed upregulation of the mu receptor (Zubieta et al., 2000).”
BackgroundCognitive function during nicotine withdrawal: Implications for nicotine dependence treatment
Ashare, R. L., Falcone, M., & Lerman, C. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.034 · Cited by 170
“Further, following cessation of smoking, unbound nAChRs are present at a higher level for as long as one week, and nAChR binding availability has been associated with self-reported withdrawal and craving (Cosgrove et al., 2009; Staley et al., 2006).”
Dual role of nicotine in addiction and cognition: A review of neuroimaging studies in humans
Jasinska, A. J., Zorick, T. S., Brody, A. L., & Stein, E. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.02.015 · Cited by 170
“…2-FA and 5-IA, have demonstrated up-regulation of available a4b2* nAChRs in smokers compared to non-smoking participants in brain regions other than the thalamus (Brody et al., 2012; Cosgrove et al., 2009, 2012; Mamede et al., 2007; Mukhin et al., 2008; Staley et al., 2006; Wullner et al., 2008).”
InfluentialLester, H. A., Xiao, C., Srinivasan, R., Son, C. D., Miwa, J., Pantoja, R., Banghart, M. R., Dougherty, D. A., Goate, A. M., & Wang, J. C. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9090-7 · Cited by 163
Cosgrove, K. P., Batis, J., Bois, F., Maciejewski, P. K., Esterlis, I., Kloczynski, T., Stiklus, S., Krishnan-Sarin, S., O’Malley, S., Perry, E., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.41 · Cited by 165
Self-citationGenetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction
Mineur, Y. S., & Picciotto, M. R. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.06.010 · Cited by 139
“Upregulation is still observed in abstinent smokers at least 14 days after smoking cessation [63], and tolerance can also be observed without changes in nicotine binding [64].”
BackgroundSelf-citationConti, D. V., Lee, W., Li, D., Liu, J., Van Den Berg, D., Thomas, P. D., Bergen, A. W., Swan, G. E., Tyndale, R. F., Benowitz, N. L., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn181 · Cited by 136
Mukhin, A. G., Kimes, A. S., Chefer, S. I., Matochik, J. A., Contoreggi, C. S., Horti, A. G., Vaupel, D. B., Pavlova, O., & Stein, E. A. (2008) · Journal of Nuclear Medicine · doi:10.2967/jnumed.108.050716 · Cited by 135
“As mentioned, the observed changes in VT/fP were similar to those observed with SPECT and 5IA as the radioligand (28).”
ResultAcetylcholine receptors in dementia and mild cognitive impairment
Sabri, O., Kendziorra, K., Wolf, H., Gertz, H., & Brust, P. (2008) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-007-0701-1 · Cited by 128
“the effects of tobacco use on nicotinic receptor saturation and availability [86–91].”
BackgroundNeurobiological Mechanisms of Nicotine Reward and Aversion
Wills, L. P., Ables, J. L., Braunscheidel, K. M., Caligiuri, S. P. B., Elayouby, K. S., Fillinger, C., Ishikawa, M., Moen, J. K., & Kenny, P. J. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000299 · Cited by 134
“Nicotine-induced upregulation of nAChR expression has been detected in the brains of rodents and human smokers (Marks et al., 1983; Breese et al., 1997; Staley et al., 2006; Nashmi et al., 2007).”
BackgroundYoung, J. W., & Geyer, M. A. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.06.031 · Cited by 128
“nAChRs and commonly used in smoking studies [81,82].”
Molecules and circuits involved in nicotine addiction: The many faces of smoking
Picciotto, M. R., & Mineur, Y. S. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.028 · Cited by 123
“However, chronic smoking also leads to long-term upregulation of high affinity nAChRs containing the b2 subunit (Staley et al., 2006), potentially increasing nAChR activity once nicotine-induced desensitization is relieved following abstinence.”
BackgroundSelf-citationPersistent β 2 *-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder
Saricicek, A., Esterlis, I., Maloney, K. H., Mineur, Y. S., Ruf, B. M., Muralidharan, A., Chen, J. I., Cosgrove, K. P., Kerestes, R., Ghose, S., et al. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11101546 · Cited by 118
“SPECT imaging protocol was conducted as described previously (34).”
BackgroundMethodSelf-citationSutherland, M. T., Riedel, M. C., Flannery, J. S., Yanes, J. A., Fox, P. T., Stein, E. A., & Laird, A. R. (2016) · Behavioral and Brain Functions · doi:10.1186/s12993-016-0100-5 · Cited by 114
“Widespread upregulation of nAChRs, likely related to receptor desensitization from nicotine exposure, has been observed among smokers [70, 71] and, conversely, smoking cessation associated with decreases in regional nAChR densities [72].”
BackgroundLong-term effects of chronic nicotine exposure on brain nicotinic receptors
Besson, M., Granon, S., Mameli-Engvall, M., Cloëz-Tayarani, I., Maubourguet, N., Cormier, A., Cazala, P., David, V., Changeux, J., & Fauré, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702698104 · Cited by 117
Molecular and Cellular Mechanisms of Action of Nicotine in the CNS
Barik, J., & Wonnacott, S. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-69248-5_7 · Cited by 112
Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers
Brody, A. L., Mukhin, A. G., Charite, J. L., Ta, K., Farahi, J. B., Sugar, C. A., Mamoun, M. S., Vellios, E. E., Archie, M. M., Kozman, M., et al. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712001022 · Cited by 106
“This issue of smokers using nicotine/tobacco during the abstinence period of a brain imaging study has also been reported in prior studies (Esterlis et al. 2010a ; Staley et al. 2006), presumably related to difficulty in having tobaccodependent smokers remain abstinent for a prolonged period.”
BackgroundMethodResultInfluentialInside-out neuropharmacology of nicotinic drugs
Henderson, B. J., & Lester, H. A. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.01.022 · Cited by 109
“Upregulation of AChRs in humans has been detected by comparing [3H]nicotine binding to postmortem brains of smokers and non-smokers and in vivo by fMRI or PET imaging (Benwell et al., 1988; Breese et al., 1997; Brody et al., 2013, 2008, 2011, 2006; Cosgrove et al., 2009; Jasinska et al., 2014; Mamede et al., 2007; Per…”
Cosgrove, K. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.1465 · Cited by 109
Self-citationPerry, D. C., Mao, D., Gold, A. B., McIntosh, J. M., Pezzullo, J. C., & Kellar, K. J. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.121228 · Cited by 106
“Recently, increased nAChRs were imaged in living human subjects who smoked (Staley et al., 2006).”
BackgroundPerkins, K. A., Karelitz, J. L., Conklin, C. A., Sayette, M. A., & Giedgowd, G. E. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.12.017 · Cited by 105
Nicotine patch therapy prior to quitting smoking: a meta‐analysis
Shiffman, S., & Ferguson, S. G. (2008) · Addiction · doi:10.1111/j.1360-0443.2008.02138.x · Cited by 94
“While the terminal half-life of nicotine is ~ 2 hours [14], a recent imaging study [15] suggests that nicotine may reside on the nicotine receptor for a longer duration.”
In vivo Brain Imaging of Human Exposure to Nicotine and Tobacco
Sharma, A., & Brody, A. L. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-69248-5_6 · Cited by 90
“In a recent study, Staley et al. (2006) hypothesized that an abnormally high number of β2nAChRs in early abstinence may be responsible for continued tobacco usage.”
Temporal Change in Human Nicotinic Acetylcholine Receptor After Smoking Cessation: 5IA SPECT Study
Mamede, M., Ishizu, K., Ueda, M., Mukai, T., Iida, Y., Kawashima, H., Fukuyama, H., Togashi, K., & Saji, H. (2007) · Journal of Nuclear Medicine · doi:10.2967/jnumed.107.043471 · Cited by 91
“The authors noted that after 6.8 6 1.9 d of tobacco abstinence, the uptake of 123I-5IA increased significantly throughout the cerebral cortex (26%;36%) in smokers ( 13 ).”
BackgroundMethodResultInfluentialOvarian Hormones and Drug Abuse
Maria, M. M. M., Flanagan, J. C., & Brady, K. T. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0511-7 · Cited by 89
Henderson, B. J., Wall, T. R., Henley, B. M., Kim, C. H., Nichols, W. A., Moaddel, R., Xiao, C., & Lester, H. A. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4194-15.2016 · Cited by 79
“…using 2-[ 18F]fluoro-A-85380 (binds 2* nAChRs) indicate that 2* nAChR upregulation in humans is saturated with only a few cigarettes smoked daily (Staley et al., 2006), probably because 2* nAChRs are saturated even at nicotine concentrations found in low-nicotine cigarettes (Brody et al., 2009).”
MethodUnderstanding the habenula: A major node in circuits regulating emotion and motivation
Ables, J. L., Park, K., & Ibáñez-Tallon, I. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106734 · Cited by 79
Mineur, Y. S., Cahuzac, E. L. M., Mose, T. N., Bentham, M. P., Plantenga, M. E., Thompson, D. C., & Picciotto, M. R. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0024-x · Cited by 71
“One consequence of chronic nicotine exposure through tobacco smoke is an upregulation of high-affinity β2-containing nAChRs throughout the brain [13].”
BackgroundSelf-citationPharmacological chaperoning of nAChRs: A therapeutic target for Parkinson's disease
Srinivasan, R., Henderson, B. J., Lester, H. A., & Richards, C. I. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.02.005 · Cited by 67
Greenbaum, L., & Lerer, B. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.59 · Cited by 73
Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning
Gould, T. J., & Leach, P. T. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.08.004 · Cited by 72
Cigarette craving is associated with blunted reward processing in nicotine-dependent smokers
Peechatka, A. L., Whitton, A. E., Farmer, S. L., Pizzagalli, D. A., & Janes, A. C. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.07.015 · Cited by 67
Quaak, M., van Schayck, O. C. P., Knaapen, A. M., & van Schooten, F. (2009) · European Respiratory Journal · doi:10.1183/09031936.00056908 · Cited by 66
Brody, A. L., Hubert, R., Enoki, R., Garcia, L. Y., Mamoun, M. S., Okita, K., London, E. D., Nurmi, E. L., Seaman, L. C., & Mandelkern, M. A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.48 · Cited by 67
“…would occur globally throughout the brain, as prior research by our group (Brody et al, 2006a, 2009a, 2011, 2013) and others (Cosgrove et al, 2009; Staley et al, 2006) demonstrates widespread effects of smoking when studying systems (eg, the nicotinic cholinergic system) that are widely…”
BackgroundResultSelf-citationAge-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT
Mitsis, E. M., Cosgrove, K. P., Staley, J. K., Bois, F., Frohlich, E. B., Tamagnan, G. D., Estok, K. M., Seibyl, J. P., & van Dyck, C. H. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.12.008 · Cited by 65
Self-citationRodent models for nicotine withdrawal
Chellian, R., Behnood‐Rod, A., Bruijnzeel, D. M., Wilson, R., Pandy, V., & Bruijnzeel, A. W. (2021) · Journal of Psychopharmacology · doi:10.1177/02698811211005629 · Cited by 71
“In humans, smoking leads to an upregulation of α4β2* nAChRs in the brain (Benwell et al., 1988; Staley et al., 2006).”
BackgroundHannestad, J. O., Cosgrove, K. P., DellaGioia, N. F., Perkins, E., Bois, F., Bhagwagar, Z., Seibyl, J. P., McClure-Begley, T. D., Picciotto, M. R., & Esterlis, I. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.04.004 · Cited by 63
“Previous studies revealed that 1 week of smoking cessation is required for all nicotine to leave the brain to accurately quantify β2*nAChR availability (25).”
BackgroundSelf-citationEffects of Nicotine on the Neurophysiological and Behavioral Effects of Ketamine in Humans
Mathalon, D. H., Ahn, K.-H., Perry, E. B., Cho, H. S., Roach, B. J., Blais, R. K., Bhakta, S. G., Ranganathan, M., Ford, J. M., & D’Souza, D. C. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00003 · Cited by 64
“Plasma nicotine concentrations were assayed using reversed-phase highperformance liquid chromatography (HPLC) based on a modification of a previously described method (115, 116).”
MethodSelf-citationAddiction‐related neuroadaptations following chronic nicotine exposure
Wills, L., & Kenny, P. J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15356 · Cited by 61
Lower β2*-Nicotinic Acetylcholine Receptor Availability in Smokers With Schizophrenia
D’Souza, D. C., Esterlis, I., Carbuto, M., Krasenics, M., Seibyl, J. P., Bois, F., Pittman, B. P., Ranganathan, M., Cosgrove, K., & Staley, J. K. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11020189 · Cited by 62
Self-citationChang, D., Zhang, J., Peng, W., Shen, Z., Gao, X., Du, Y., Ge, Q., Song, D., Shang, Y., & Wang, Z. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00344 · Cited by 54
“Due to the chronic nAchRs upregulation, abstinence from nicotine will dramatically increase the availability of unbound α4β2 nAchRs, which in turn leads to smoking craving (Staley et al., 2006) and the subsequent smoking relapse.”
BackgroundSabri, O., Becker, G., Meyer, P., Hesse, S., Wilke, S., Graef, S., Patt, M., Luthardt, J., Wagenknecht, G., Hoepping, A., et al. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.05.065 · Cited by 59
“, 2006), nicotine dependence (Mukhin et al., 2008; Staley et al., 2006), major depressive disease (Saricicek et al.”
Nicotinic Receptor Contributions to Smoking: Insights from Human Studies and Animal Models
Brunzell, D. H., Stafford, A. M., & Dixon, C. I. (2015) · Current Addiction Reports · doi:10.1007/s40429-015-0042-2 · Cited by 58
Therapeutic vaccines against tobacco addiction
Fahim, R. E. F., Kessler, P., & Kalnik, M. W. (2013) · Expert Review of Vaccines · doi:10.1586/erv.13.13 · Cited by 57
Nicotine Dependence: Biology, Behavior, and Treatment
Ray, R., Schnoll, R. A., & Lerman, C. E. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.041707.160511 · Cited by 59
“The same study demonstrated that abstinence-induced increases in the numbers of unbound receptors correlated with smoking urges (26).”
BackgroundLindroos, R., Dorst, M. C., Du, K., Filipović, M., Keller, D. X., Ketzef, M., Kozlov, A., Kumar, A., Lindahl, M., Nair, A. G., et al. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00003 · Cited by 44
“As ACh and DA Frontiers in Neural Circuits | www.frontiersin.org 4 February 2018 | Volume 12 | Article 3 are believed to serve antagonistic roles, increasing cholinergic tone through acetylcholinesterase inhibitors can suppress addictive symptoms (Staley et al., 2006).”
BackgroundGould, T. J., Portugal, G. S., André, J. M., Tadman, M. P., Marks, M. J., Kenney, J. W., Yildirim, E., & Adoff, M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.01.003 · Cited by 56
“Abstinent smokers compared to nonsmokers had higher levels of b2* nAChRs, which returned to baseline between 3e12 weeks, and elevated nAChR levels correlated with urge to smoke (Cosgrove et al., 2009; Mamede et al., 2007; Staley et al., 2006).”
The nicotinic cholinergic system function in the human brain
Nees, F. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.021 · Cited by 57
Esterlis, I., Ranganathan, M., Bois, F., Pittman, B. P., Picciotto, M. R., Shearer, L., Anticevic, A., Carlson, J., Niciu, M. J., Cosgrove, K., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.11.001 · Cited by 53
Self-citationRegional metabolite levels and turnover in the awake rat brain under the influence of nicotine
Wang, J., Jiang, L., Jiang, Y., Ma, X., Chowdhury, G. M. I., & Mason, G. F. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06684.x · Cited by 53
“Though there are some differences, such as a subunit distribution in the thalamus, reviewed previously (Spurden et al. 1997), they are in general similarly distributed in rats and humans (Spurden et al. 1997; Turner and Kellar 2005; Staley et al. 2006).”
BackgroundEsterlis, I., Hannestad, J. O., Perkins, E., Bois, F., D’Souza, D. C., Tyndale, R. F., Seibyl, J. P., Hatsukami, D., Cosgrove, K., & O’Malley, S. S. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12060793 · Cited by 55
Self-citationThe Molecular and Cellular Neurobiology of Nicotine Abuse in Schizophrenia
Mobascher, A., & Winterer, G. (2008) · Pharmacopsychiatry · doi:10.1055/s-2008-1081463 · Cited by 50
Poorthuis, R. B., & Mansvelder, H. D. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.07.003 · Cited by 54
“Imaging studies showed that receptors remain upregulated even in the abstinence of smoking for more than seven days [139].”
BackgroundNicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement
Morel, C., Montgomery, S. E., & Han, M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14160 · Cited by 50
Kimes, A. S., Chefer, S. I., Matochik, J. A., Contoreggi, C. S., Vaupel, D. B., Stein, E. A., & Mukhin, A. G. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.09.015 · Cited by 49
In vivo measurement of nicotinic acetylcholine receptors with [18F]norchloro‐fluoro‐homoepibatidine
Brust, P., Patt, J. T., Deuther‐Conrad, W., Becker, G., Patt, M., Schildan, A., Sorger, D., Kendziorra, K., Meyer, P., Steinbach, J., et al. (2007) · Synapse · doi:10.1002/syn.20480 · Cited by 46
“…nicotinic receptor saturation and availability in volunteers (Brody et al., 2006; Gallezot et al., 2005; Kimes et al., 2003; Shumway et al., 2007; Staley et al., 2005, 2006), only a few studies were performed in patients which show alterations in nAChRs densities in frontal lobe epilepsy (Picard…”
BackgroundPathophysiology of nAChRs: Limbic circuits and related disorders
Mineur, Y. S., Soares, A. R., Etherington, I. M., Abdulla, Z. I., & Picciotto, M. R. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106745 · Cited by 42
Self-citationMenossi, H. S., Goudriaan, A. E., Périco, C. D. A.-M., Nicastri, S., de Andrade, A. G., D’Elia, G., Li, C. R., & Castaldelli-Maia, J. M. (2013) · CNS Drugs · doi:10.1007/s40263-013-0092-8 · Cited by 48
“In abstinent smokers, the level of free a4b2 nAChRs is associated with the desire to smoke [29].”
BackgroundBrain Nicotinic Acetylcholine Receptor Availability and Response to Smoking Cessation Treatment
Brody, A. L., Mukhin, A. G., Mamoun, M. S., Luu, T., Neary, M. K., Liang, L., Shieh, J., Sugar, C. A., Rose, J. E., & Mandelkern, M. A. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.138 · Cited by 44
Nicotinic Receptors, Memory, and Hippocampus
Kutlu, M. G., & Gould, T. J. (2015) · Current topics in behavioral neurosciences · doi:10.1007/978-3-319-13665-3_6 · Cited by 42
Verplaetse, T. L., Morris, E. D., McKee, S. A., & Cosgrove, K. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.04.004 · Cited by 41
Self-citationImaging Receptor Changes in Human Drug Abusers
Cosgrove, K. (2009) · Current topics in behavioral neurosciences · doi:10.1007/7854_2009_24 · Cited by 41
“Specifically, there is a higher availability of b2*-nAChRs in tobacco smokers during acute abstinence compared to never smokers in the cerebellum, striatum, and throughout the cortex (Mukhin et al. 2008; Staley et al. 2006).”
BackgroundSelf-citationLewis, A. S., & Picciotto, M. R. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3126-5 · Cited by 38
“This study was done in recently abstinent (~1 week) tobacco smokers, since the nicotine from tobacco competes with the radiotracer, and previous studies have shown that there is still upregulation of nAChRs at this time point in smokers without psychiatric illness (Staley et al. 2006).”
InfluentialSelf-citationTobacco smoking and dopaminergic function in humans: a meta-analysis of molecular imaging studies
Ashok, A. H., Mizuno, Y., & Howes, O. D. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05196-1 · Cited by 36
“Moreover, molecular imaging studies have shown that occupancy of the nicotinic acetylcholine receptor is associated with the subjective hedonic response of smoking (Brody et al. 2009a, 2011, 2006a, 2014, 2013; Cosgrove et al. 2009a; Cosgrove et al. 2012; Dubroff et al. 2015; Lotfipour et al. 2012; Staley et al. 2006).”
BackgroundD’Souza, D. C., Ahn, K.-H., Bhakta, S. G., Elander, J., Singh, N. M., Nadim, H., Jatlow, P. I., Suckow, R. F., Pittman, B. P., & Ranganathan, M. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.05.009 · Cited by 38
Self-citationLong-Term Upregulation of Protein Kinase A and Adenylate Cyclase Levels in Human Smokers
Hope, B. T., Nagarkar, D. R., Leonard, S. S., & Wise, R. A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3661-06.2007 · Cited by 37
Neuropeptide systems and new treatments for nicotine addiction
Bruijnzeel, A. W. (2017) · Psychopharmacology · doi:10.1007/s00213-016-4513-5 · Cited by 36
“Tobacco use in humans and chronic nicotine or tobacco smoke exposure in rodents leads to an upregulation of nAChRs in the brain (Benwell et al. 1988; Marks et al. 1983; Small et al. 2010; Staley et al. 2006).”
Cosgrove, K., Esterlis, I., McKee, S. A., Bois, F., Alagille, D., Tamagnan, G. D., Seibyl, J. P., Krishnan‐Sarin, S., & Staley, J. K. (2010) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntq040 · Cited by 37
Self-citationKnott, V., Millar, A., McIntosh, J. F., Shah, D. K., Fisher, D. J., Blais, C. M., Ilivitsky, V., & Horn, E. (2011) · Biological Psychology · doi:10.1016/j.biopsycho.2011.06.012 · Cited by 37
Esterlis, I., Cosgrove, K., Batis, J. C., Bois, F., Stiklus, S. M., Perkins, E., Seibyl, J. P., Carson, R. E., & Staley, J. K. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.109.072447 · Cited by 36
Self-citationMcClure‐Begley, T. D., Papke, R. L., Stone, K. L., Stokes, C. A., Levy, A. D., Gelernter, J. E., Xie, P., Lindstrom, J. M., & Picciotto, M. R. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.209767 · Cited by 26
“Upregulation of a4b2* nAChRs by long-term exposure to nicotine has been suggested to play a role in the development/ maintenance of nicotine dependence and has been observed repeatedly both in vitro and in vivo in rodents and human smokers (Staley et al., 2006; Lester et al., 2009).”
BackgroundSelf-citationJørgensen, K. N., Psychol, C., Skjærvø, I., Mørch-Johnsen, L. E., Haukvik, U. K., Lange, E. H., Melle, I. S., Andreassen, O. A., & Agartz, I. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.140163 · Cited by 32
Hussmann, G. P., Turner, J. R., Lomazzo, E., Venkatesh, R., Cousins, V., Xiao, Y., Yasuda, R. P., Wolfe, B. B., Perry, D. C., Rezvani, A. H., et al. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.198085 · Cited by 34
“441 1992; Mao et al., 2008; Moretti et al., 2010; Marks et al., 2011), and based on the limited spectrum of the radioligand used to image the receptors in vivo that is also probably the case in primate brains (Kassiou et al., 2001; Staley et al., 2006; Wüllner et al., 2008).”
InfluentialBrody, A. L., Gehlbach, D. L., Garcia, L. Y., Enoki, R., Hoh, C. K., Vera, D. R., Kotta, K. K., London, E. D., Okita, K., Nurmi, E. L., et al. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5077-3 · Cited by 32
Self-citationNeurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse
Schmidt, H. D., Rupprecht, L. E., & Addy, N. (2018) · Complex Psychiatry · doi:10.1159/000494799 · Cited by 33
Archie, S. R., Sharma, S., Burks, E., & Abbruscato, T. J. (2022) · NeuroToxicology · doi:10.1016/j.neuro.2022.02.002 · Cited by 33
Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density
Brody, A. L., Mukhin, A. G., Shulenberger, S., Mamoun, M. S., Kozman, M., Phuong, J., Neary, M. K., Luu, T., & Mandelkern, M. A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.53 · Cited by 33
“…(Brody et al, 2013) and other studies linking nicotine (Marks et al, 2011; Yates et al, 1995; Zhang et al, 2002) and cigarette smoke (Mamede et al, 2007; Mukhin et al, 2008; Staley et al, 2006; Wullner et al, 2008) exposure with upregulation of a4b2* nAChRs in brain regions other than the thalamus.”
BackgroundFood Addiction and Tobacco Use Disorder: Common Liability and Shared Mechanisms
Zawertailo, L. A., Attwells, S., deRuiter, W. K., Le, T. L., Dawson, D., & Selby, P. L. (2020) · Nutrients · doi:10.3390/nu12123834 · Cited by 37
“Preclinical studies assessing nicotine administration in animals and postmortem human studies of smokers demonstrated β2-nAChR upregulation throughout the striatum, frontal cortex, anterior cingulate cortex, temporal cortex, occipital cortex, and cerebellum [73], suggesting greater levels of β2-nAChR desensitization a…”
BackgroundFasoli, F., Moretti, M., Zoli, M., Pistillo, F., Crespi, A., Clementi, F., McClure‐Begley, T. D., Marks, M. J., & Gotti, C. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.04.048 · Cited by 34
Cosgrove, K. P., Mitsis, E. M., Bois, F., Frohlich, E., Tamagnan, G. D., Krantzler, E., Perry, E., Maciejewski, P. K., Epperson, C. N., Allen, S., et al. (2007) · Journal of Nuclear Medicine · doi:10.2967/jnumed.107.042317 · Cited by 31
“High test–retest reliability and validity were recently reported for 123I-5-IA SPECT (22), and 123I-5-IA SPECT has demonstrated significantly higher b2-nAChR availability in recently abstinent tobacco smokers than in age- and sex-matched nonsmokers (23).”
BackgroundSelf-citationDecreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism
Dubroff, J. G., Doot, R. K., Falcone, M., Schnoll, R. A., Ray, R., Tyndale, R. F., Brody, A. L., Hou, C., Schmitz, A. M. T., & Lerman, C. E. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.155002 · Cited by 31
“SPECT molecular imaging studies of the nAChR a4b2* subtype have also shown that nAChR availability in smokers peaks after 1 wk of abstinence (22,24), suggesting the persistent occupation of nAChRs by nicotine.”
BackgroundLiu, W., & Li, M. D. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170801103009 · Cited by 28
“Long-term exposure to nicotine leads to an activity increase, amount upregulation, or both of nicotine binding sites in the brain of smokers [153, 154] and rodents subjected to repeated nicotine administration [155, 156].”
BackgroundYohn, N. L., Turner, J. R., & Blendy, J. A. (2014) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.211706 · Cited by 28
“…Marks et al., 1992; Buisson and Bertrand, 2002) and has been confirmed in several systems including cultured cells and rodent and human tissues (Marks et al., 1983; Schwartz and Kellar, 1985; Benwell et al., 1988; Peng et al., 1994; Breese et al., 1997; Perry et al., 1999; Staley et al., 2006).”
BackgroundNeuroimaging, genetics and the treatment of nicotine addiction
Ray, R., Loughead, J., Wang, Z., Detre, J. A., Yang, E., Gur, R. C., & Lerman, C. E. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.05.021 · Cited by 29
Imaging Tobacco Smoking with PET and SPECT
Cosgrove, K., Esterlis, I., Sandiego, C. M., Petrulli, J. R., & Morris, E. D. (2015) · Current topics in behavioral neurosciences · doi:10.1007/978-3-319-13482-6_1 · Cited by 32
“At one week of abstinence, β2*-nAChR availability in the sensorimotor cortex was negatively correlated with the urge to smoke to relieve withdrawal symptoms (Staley et al. 2006).”
BackgroundMethodResultInfluentialSelf-citationArora, K., Alfulaij, N., Higa, J. K., Panee, J., & Nichols, R. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.453746 · Cited by 29
Arias, H. R., Targowska‐Duda, K. M., García‐Colunga, J., & Ortells, M. O. (2021) · Molecules · doi:10.3390/molecules26082149 · Cited by 30
“A common feature in both conditions is that of higher ACh concentrations compared to those in the normal population [20,30,31].”
Background
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.
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