This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (64)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Psychiatry, Other  • Public Health  • Tobacco  • Alert me on articles by topic  Social Bookmarking   What's this?

Cigarette Smoking Saturates Brain ₄₂ Nicotinic Acetylcholine Receptors

Arthur L. Brody, MD; Mark A. Mandelkern, MD, PhD; Edythe D. London, PhD; Richard E. Olmstead, PhD; Judah Farahi, PhD; David Scheibal, BS; Jennifer Jou, BS; Valerie Allen, BS; Emmanuelle Tiongson, BS; Svetlana I. Chefer, PhD; Andrei O. Koren, PhD; Alexey G. Mukhin, MD, PhD

Arch Gen Psychiatry. 2006;63:907-914.

Context  2-[¹⁸F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2-F-A-85380, abbreviated as 2-FA) is a recently developed radioligand that allows for visualization of brain ₄₂* nicotinic acetylcholine receptors (nAChRs) with positron emission tomography (PET) scanning in humans.

Objective  To determine the effect of cigarette smoking on ₄₂* nAChR occupancy in tobacco-dependent smokers.

Design  Fourteen 2-FA PET scanning sessions were performed. During the PET scanning sessions, subjects smoked 1 of 5 amounts (none, 1 puff, 3 puffs, 1 full cigarette, or to satiety [2 to 3 cigarettes]).

Setting  Academic brain imaging center.

Participants  Eleven tobacco-dependent smokers (paid volunteers).

Main Outcome Measure  Dose-dependent effect of smoking on occupancy of ₄₂* nAChRs, as measured with 2-FA and PET in nAChR-rich brain regions.

Results  Smoking 0.13 (1 to 2 puffs) of a cigarette resulted in 50% occupancy of ₄₂* nAChRs for 3.1 hours after smoking. Smoking a full cigarette (or more) resulted in more than 88% receptor occupancy and was accompanied by a reduction in cigarette craving. A venous plasma nicotine concentration of 0.87 ng/mL (roughly 1/25th of the level achieved in typical daily smokers) was associated with 50% occupancy of ₄₂* nAChRs.

Conclusions  Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of ₄₂* nAChRs, indicating that tobacco-dependent smokers maintain ₄₂* nAChR saturation throughout the day. Because prolonged binding of nicotine to ₄₂* nAChRs is associated with desensitization of these receptors, the extent of receptor occupancy found herein suggests that smoking may lead to withdrawal alleviation by maintaining nAChRs in the desensitized state.

Author Affiliations: Department of Psychiatry and Biobehavioral Sciences (Drs Brody and London, Mr Scheibal, and Mss Jou, Allen, and Tiongson), University of California, Los Angeles; Greater Los Angeles Veterans Affairs Healthcare System Positron Emission Tomography Center (Drs Brody, Mandelkern, London, Olmstead, and Farahi, Mr Scheibal, and Mss Jou, Allen, and Tiongson), Los Angeles; Department of Physics, University of California, Irvine (Dr Mandelkern); Intramural Research Program, Neuroimaging Research Branch, National Institute on Drug Abuse, Rockville, Md (Drs Chefer and Mukhin); and Institute for Neurodegenerative Disorders, New Haven, Conn (Dr Koren).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions
Paulson et al.
J. Pharmacol. Exp. Ther. 2010;332:371-379.
ABSTRACT | FULL TEXT  

Abuse Liability Assessment of Tobacco Products Including Potential Reduced Exposure Products
Carter et al.
Cancer Epidemiol. Biomarkers Prev. 2009;18:3241-3262.
ABSTRACT | FULL TEXT  

Treating Tobacco Dependence in a Medical Setting
Hurt et al.
CA Cancer J Clin 2009;59:314-326.
ABSTRACT | FULL TEXT  

Reduced {alpha}4{beta}2*-Nicotinic Acetylcholine Receptor Binding and Its Relationship to Mild Cognitive and Depressive Symptoms in Parkinson Disease
Meyer et al.
Arch Gen Psychiatry 2009;66:866-877.
ABSTRACT | FULL TEXT  

{beta}2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking
Cosgrove et al.
Arch Gen Psychiatry 2009;66:666-676.
ABSTRACT | FULL TEXT  

Acute Alcohol Action and Desensitization of Ligand-Gated Ion Channels
Dopico and Lovinger
Pharmacol. Rev. 2009;61:98-114.
ABSTRACT | FULL TEXT  

Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380
Mukhin et al.
JNM 2008;49:1628-1635.
ABSTRACT | FULL TEXT  

Nicotine and Postoperative Management of Pain
Benowitz
Anesth. Analg. 2008;107:739-741.
FULL TEXT  

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors
Kassam et al.
J. Neurosci. 2008;28:8756-8764.
ABSTRACT | FULL TEXT  

Roles of Accessory Subunits in {alpha}4{beta}2* Nicotinic Receptors
Kuryatov et al.
Mol. Pharmacol. 2008;74:132-143.
ABSTRACT | FULL TEXT  

Up-regulation of Nicotinic Receptors by Nicotine Varies with Receptor Subtype
Walsh et al.
J. Biol. Chem. 2008;283:6022-6032.
ABSTRACT | FULL TEXT  

Neural Substrates of Abstinence-Induced Cigarette Cravings in Chronic Smokers
Wang et al.
J. Neurosci. 2007;27:14035-14040.
ABSTRACT | FULL TEXT  

Temporal Change in Human Nicotinic Acetylcholine Receptor After Smoking Cessation: 5IA SPECT Study
Mamede et al.
JNM 2007;48:1829-1835.
ABSTRACT | FULL TEXT  

The Endocannabinoid Anandamide Inhibits the Function of {alpha}4beta2 Nicotinic Acetylcholine Receptors
Spivak et al.
Mol. Pharmacol. 2007;72:1024-1032.
ABSTRACT | FULL TEXT  

Symptoms of Tobacco Dependence After Brief Intermittent Use: The Development and Assessment of Nicotine Dependence in Youth-2 Study
DiFranza et al.
Arch Pediatr Adolesc Med 2007;161:704-710.
ABSTRACT | FULL TEXT  

Smoking kills (alcoholics)! shouldn't we do something about it?
Littleton et al.
Alcohol Alcohol 2007;42:167-173.
ABSTRACT | FULL TEXT  

Sazetidine-A, A Novel Ligand That Desensitizes {alpha}4beta2 Nicotinic Acetylcholine Receptors without Activating Them
Xiao et al.
Mol. Pharmacol. 2006;70:1454-1460.
ABSTRACT | FULL TEXT