title: Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence.
abstract: This paper reviews evidence suggesting that nicotine and tobacco smoke profoundly modulate the effects of alcohol on γ-aminobutyric acid (GABA) neuronal function, specifically at the GABA(A)-benzodiazepine receptor (GABA(A)-BZR). The focus of this paper is on recent neuroimaging evidence in preclinical models as well as clinical experiments. First, we review findings implicating the role of alcohol at the GABA(A)-BZR and discuss the changes in GABA(A)-BZR availability during acute and prolonged alcohol withdrawal. Second, we discuss preclinical evidence that suggests nicotine affects GABA neuronal function indirectly by a primary action at neuronal nicotinic acetylcholine receptors. Third, we show how this evidence converges in studies that examine GABA levels and GABA(A)-BZRs in alcohol-dependent smokers and nonsmokers, suggesting that tobacco smoking attenuates the chemical changes that occur during alcohol withdrawal. Based on a comprehensive review of literature, we hypothesize that tobacco smoking minimizes the changes in GABA levels that typically occur during the acute cycles of drinking in alcohol-dependent individuals. Thus, during alcohol withdrawal, the continued tobacco smoking decreases the severity of the withdrawal-related changes in GABA chemistry. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine and the VACHS, West Haven, CT 06516, USA. kelly.cosgrove@yale.edu
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Mason
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
mesh_terms: D000437:Alcoholism / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000534:rehabilitation; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011877:Radionuclide Imaging; D011963:Receptors, GABA-A / Q000378:metabolism; D012907:Smoking; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018722:Nicotinic Agonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D009538:Nicotine