title: Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal.
abstract: Understanding the effects of tobacco smoking on neuroadaptations in GABAA receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABAA receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABAA receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABAA receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABAA receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABAA receptor levels normalized by 1 mo of abstinence in both groups--that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABAA receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking.
authors.affiliation: Departments of Psychiatry and Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT 06516; National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06510; Neurobiology, and Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT 06510; kelly.cosgrove@yale.edu.
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.affiliation: Departments of Psychiatry and Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT 06114; and.
authors.forename: Reese
authors.initials: R
authors.lastname: McKay
authors.affiliation: Departments of Psychiatry and Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT 06516; National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06510; Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.affiliation: Departments of Psychiatry and.
authors.forename: Tracy
authors.initials: T
authors.lastname: Kloczynski
authors.affiliation: Departments of Psychiatry and.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Perkins
authors.affiliation: Departments of Psychiatry and.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.affiliation: Departments of Psychiatry and National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06510;
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center San Antonio, 78229.
authors.forename: Jack
authors.initials: J
authors.lastname: Lancaster
authors.affiliation: Departments of Psychiatry and Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT 06114; and.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: Departments of Psychiatry and National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06510;
authors.forename: Stephanie
authors.initials: S
authors.lastname: O'Malley
authors.affiliation: Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Departments of Psychiatry and Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT 06516; National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06510; Neurobiology, and.
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002250:Carbon Radioisotopes; D066249:Craving / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives; D006801:Humans; D007457:Iodine Radioisotopes; D008253:Macaca mulatta; D008297:Male; D009538:Nicotine / Q000009:adverse effects*; D049268:Positron-Emission Tomography; D011963:Receptors, GABA-A / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; D009538:Nicotine; C063038:iomazenil
keywords: GABAA receptors; alcohol dependence; neuroimaging; tobacco smoking; translational