beta2-Nicotinic acetylcholine receptor availability during acute and prolonged abstinence from tobacco smoking.

paper Cited Public

Authors: Cosgrove, Kelly P; Batis, Jeffery; Bois, Frederic; Maciejewski, Paul K; Esterlis, Irina; Kloczynski, Tracy; Stiklus, Stephanie; Krishnan-Sarin, Suchitra; O'Malley, Stephanie; Perry, Edward; Tamagnan, Gilles; Seibyl, John P; Staley, Julie K
Year: 2009
Journal: Archives of general psychiatry
PMID: 19487632
DOI: 10.1001/archgenpsychiatry.2009.41
PMCID: PMC2796827

CONTEXT: Available levels of nicotinic acetylcholine receptors containing the beta(2) subunit (beta(2)*-nAChR) are higher in recently abstinent tobacco smokers compared with participants who never smoked. Variations in beta(2)*-nAChR availability during the course of abstinence may be related to the urge to smoke, the extent of nicotine withdrawal, and successful abstinence. OBJECTIVE: To examine changes in beta(2)*-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in beta(2)*-nAChR availability were related to clinical features of tobacco smoking. DESIGN: Tobacco smokers participated in up to 4 iodide 123-labeled 5-iodo-A-85380 ([(123)I]5-IA) single-photon emission computed tomography (SPECT) scans during abstinence at 1 day (n = 7) and 1 (n = 17), 2 (n = 7), 4 (n = 11), and 6 to 12 (n = 6) weeks. Age-matched nonsmokers participated in a single [(123)I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. SETTING: Academic imaging center. PARTICIPANTS: Tobacco smokers (n = 19) and an age-matched nonsmoker comparison group (n = 20). Main Outcome Measure The [(123)I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest. RESULTS: Compared with nonsmokers, beta(2)*-nAChR availability in the striatum, cortex, and cerebellum of smokers was not different at 1 day of abstinence, was significantly higher at 1 week of abstinence, and was not different at 4 or at 6 to 12 weeks of abstinence. In smokers, beta(2)*-nAChR availability was significantly lower in the cortex and cerebellum at 6 to 12 weeks compared with 1 week of abstinence. In addition, cerebellar beta(2)*-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of the SPECT scan. CONCLUSIONS: These data suggest that higher beta(2)*-nAChR availability persists up to 1 month of abstinence and normalizes to nonsmoker levels by 6 to 12 weeks of abstinence from tobacco smoking. These marked and persistent changes in beta(2)*-nAChR availability may contribute to difficulties with tobacco cessation.

#	Section	Preview
0	Methods — Subjects	Nineteen healthy tobacco smokers (9 men, 10 women; 41.1±9.0 years; 13 Caucasian, 5 African…
1	Methods — Subjects	This study was approved by the Yale University School of Medicine Human Investigation Committee, the…
2	Methods — Subjects	least one year. Smoking status was confirmed by plasma cotinine levels >150 ng/mL, urine cotinine…
3	Methods — Subjects	ng/mL and carbon monoxide levels <11 ppm on the day of intake and day of scan. All women were…
4	Methods — Subjects	The severity of nicotine dependence was assessed at intake with the Fagerström Test for Nicotine…
5	Methods — MR Imaging	MRI studies were obtained on a 1.5 Tesla Siemens camera in a standard orientation (TE=5-7 ms;…
6	Methods — [123I]5-IA SPECT scan	All subjects received a 0.6-g saturated solution of potassium iodide, to protect their thyroid from…
7	Methods — [123I]5-IA SPECT scan	infusion on a Picker PRISM 3000 XP (Cleveland, OH) SPECT camera. The PRISM 3000 XP is a 3-headed…
8	Methods — Image analysis and outcome measures	Images were reconstructed and analyzed as previously described including a nonuniform attenuation…
9	Methods — Image analysis and outcome measures	The outcome measure VT/fP (regional activity divided by free plasma parent between 6 and 8 hours),…
10	Methods — Statistical Analyses	Data were analyzed using SAS version 9.1 (SAS Institute Inc, Cary, NC). Differences in blood…
11	Methods — Statistical Analyses	examining between-group differences for which there was a significant effect of group, four planned…
12	Results — Clinical population	Nineteen tobacco smokers and 20 age-matched nonsmokers were included in the study. Smokers who…
13	Results — β2*-nAChR availability during acute and prolonged abstinence	There were no differences between groups in injected dose, bolus to infusion ratio, or time of scan…
14	Results — β2*-nAChR availability during acute and prolonged abstinence	Regional β2*-nAChR availability, reflected by VT/fP, was compared between nonsmokers and each of…
15	Results — β2*-nAChR availability during acute and prolonged abstinence	Among the abstinent smoker groups, there were significant between group differences in VT/fP in the…
16	Results — Relationship between β2*-nAChR availability and clinical features	There were significant differences in QSU-Intent (F[4,25]=7.41, p<0.015) and QSU Relief…
17	Results — Relationship between β2*-nAChR availability and clinical features	There were significant correlations between regional β2*-nAChR availability and clinical features…
18	Comment	The present study examined the time course of changes in β2*-nAChR availability during acute and…
19	Comment	these results. First, at 1 day of abstinence there is still residual nicotine, or a…

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A Control Theory Model of Smoking.	Bobashev G et al.	—	2017	→
A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke.	Jensen KP et al.	—	2017	→
Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [<sup>11</sup>C]DAA1106 Positron Emission Tomography Study.	Brody AL et al.	—	2017	→
Effects of ceftriaxone on conditioned nicotine reward in rats.	Philogene-Khalid HL et al.	—	2017	→
Epigenetic dysregulation of protocadherins in human disease.	El Hajj N et al.	—	2017	→
Human biodistribution and dosimetry of [<sup>18</sup>F]nifene, an α4β2* nicotinic acetylcholine receptor PET tracer.	Betthauser TJ et al.	—	2017	→
In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.	Jackson A et al.	—	2017	→
Negative affect subtypes and craving differentially predict long-term cessation success among smokers achieving initial abstinence.	Zuo Y et al.	—	2017	→
Nicotinic modulation of salience network connectivity and centrality in schizophrenia.	Smucny J et al.	—	2017	→
Regular moist snuff dipping does not affect endurance exercise performance.	Björkman F et al.	—	2017	→
Selective and regulated trapping of nicotinic receptor weak base ligands and relevance to smoking cessation.	Govind AP et al.	—	2017	→
A Need for Longitudinal Studies in the Addiction Field.	Cosgrove KP	—	2016	→
CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation.	Esterlis I et al.	—	2016	→
Imaging of cerebral α4β2* nicotinic acetylcholine receptors with (-)-[(18)F]Flubatine PET: Implementation of bolus plus constant infusion and sensitivity to acetylcholine in human brain.	Hillmer AT et al.	—	2016	→
In vivo chronic nicotine exposure differentially and reversibly affects upregulation and stoichiometry of α4β2 nicotinic receptors in cortex and thalamus.	Fasoli F et al.	—	2016	→
nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives.	Parikh V et al.	—	2016	→
Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use.	Brody AL et al.	—	2016	→
Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.	Simmons SJ et al.	—	2016	→
An audit of assessment and outcome of intervention at a quit smoking clinic in a homeless hostel.	Power J et al.	—	2015	→
Anxiolytic-like and anxiogenic-like effects of nicotine are regulated via diverse action at β2*nicotinic acetylcholine receptors.	Anderson SM et al.	—	2015	→
Contributions of β2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice.	Cole RD et al.	—	2015	→
Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.	Dubroff JG et al.	—	2015	→
Effects of Menthol on Nicotine Pharmacokinetic, Pharmacology and Dependence in Mice.	Alsharari SD et al.	—	2015	→
Imaging Tobacco Smoking with PET and SPECT.	Cosgrove KP et al.	—	2015	→
Inside-out neuropharmacology of nicotinic drugs.	Henderson BJ et al.	—	2015	→
Nicotinic receptor contributions to smoking: insights from human studies and animal models.	Brunzell DH et al.	—	2015	→
The nicotinic cholinergic system function in the human brain.	Nees F	—	2015	→
Withdrawal: Expanding a Key Addiction Construct.	Piper ME	—	2015	→
Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial.	Brody AL et al.	—	2014	→
Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.	Hillmer AT et al.	—	2014	→
Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain.	Hussmann GP et al.	—	2014	→
Cognitive function during nicotine withdrawal: Implications for nicotine dependence treatment.	Ashare RL et al.	—	2014	→
Donepezil reverses nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6J mice.	Poole RL et al.	—	2014	→
Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans.	Jasinska AJ et al.	—	2014	→
Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia.	Boggs DL et al.	—	2014	→
How to design PET experiments to study neurochemistry: application to alcoholism.	Morris ED et al.	—	2014	→
Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity.	Trifilieff P et al.	—	2014	→
In vivo evidence for β2 nicotinic acetylcholine receptor subunit upregulation in smokers as compared with nonsmokers with schizophrenia.	Esterlis I et al.	—	2014	→
Involvement of neuronal β2 subunit-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal: implications for pharmacotherapies.	Simmons SJ et al.	—	2014	→
Nicotine administration in healthy non-smokers reduces appetite but does not alter plasma ghrelin.	Pilhatsch M et al.	—	2014	→
Ovarian hormones and drug abuse.	Moran-Santa Maria MM et al.	—	2014	→
Pharmacological chaperoning of nAChRs: a therapeutic target for Parkinson's disease.	Srinivasan R et al.	—	2014	→
Smoking cessation in men and women.	Potter AS	—	2014	→
Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.	Turner JR et al.	—	2013	→
Effect of a nicotine vaccine on nicotine binding to β2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers.	Esterlis I et al.	—	2013	→
Measuring α4β2* nicotinic acetylcholine receptor density in vivo with [(18)F]nifene PET in the nonhuman primate.	Hillmer AT et al.	—	2013	→
Passive Response to Stress in Adolescent Female and Adult Male Mice after Intermittent Nicotine Exposure in Adolescence.	Thanos P et al.	—	2013	→
Radiosynthesis of racemic and enantiomerically pure (-)-[18F]flubatine--a promising PET radiotracer for neuroimaging of α4β2 nicotinic acetylcholine receptors.	Fischer S et al.	—	2013	→
Translational research in nicotine dependence.	Turner JR et al.	—	2013	→
Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density.	Brody AL et al.	—	2013	→
Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers.	Brody AL et al.	—	2013	→
A cognitive phenotype for a polymorphism in the nicotinic receptor gene CHRNA4.	Greenwood PM et al.	—	2012	→
Lower ß2*-nicotinic acetylcholine receptor availability in smokers with schizophrenia.	D'Souza DC et al.	—	2012	→
Nicotinic acetylcholine receptor expression on B-lymphoblasts of healthy versus schizophrenic subjects stratified for smoking: [3H]-nicotine binding is decreased in schizophrenia and correlates with negative symptoms.	Luckhaus C et al.	—	2012	→
Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder.	Saricicek A et al.	—	2012	→
Reward sensitization: effects of repeated nicotine exposure and withdrawal in mice.	Hilario MR et al.	—	2012	→
Selegiline transdermal system (STS) as an aid for smoking cessation.	Kahn R et al.	—	2012	→
Sex differences in availability of β2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers.	Cosgrove KP et al.	—	2012	→
Smoking, quitting, and psychiatric disease: a review.	Aubin HJ et al.	—	2012	→
The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation.	Gould TJ et al.	—	2012	→
Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain.	Brody AL et al.	—	2011	→
Parallel anxiolytic-like effects and upregulation of neuronal nicotinic acetylcholine receptors following chronic nicotine and varenicline.	Turner JR et al.	—	2011	→
Progress and challenges in the study of α6-containing nicotinic acetylcholine receptors.	Letchworth SR et al.	—	2011	→
Quantitative Molecular Imaging of Neuronal Nicotinic Acetylcholine Receptors in the Human Brain with A-85380 Radiotracers.	Lotfipour S et al.	—	2011	→
Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence.	Xie P et al.	—	2011	→
Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention.	Knott VJ et al.	—	2011	→
Smoking and Neuroimaging: A Review.	Kober H et al.	—	2011	→
Beta2* nicotinic acetylcholine receptors modulate pain sensitivity in acutely abstinent tobacco smokers.	Cosgrove KP et al.	—	2010	→
Brain imaging of nicotinic receptors in Alzheimer's disease.	Wu J et al.	—	2010	→
Craving among long-abstinent smokers: an Internet survey.	Hughes JR	—	2010	→
Effects of the alpha4beta2 partial agonist varenicline on brain activity and working memory in abstinent smokers.	Loughead J et al.	—	2010	→
Imaging receptor changes in human drug abusers.	Cosgrove KP	—	2010	→
Quantification of smoking-induced occupancy of beta2-nicotinic acetylcholine receptors: estimation of nondisplaceable binding.	Esterlis I et al.	—	2010	→
SPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals.	Esterlis I et al.	—	2010	→
Why do patients with schizophrenia smoke?	Winterer G	—	2010	→