Tobacco smoking interferes with gabaa receptor neuroadaptations during prolonged alcohol withdrawal

Kelly P. Cosgrove, Reese McKay, Irina Esterlis, Tracy Kloczynski, Evgenia Perkins, Frederic Bois, Brian Pittman, Jack Lancaster, David C. Glahn, Stephanie O'Malley, Richard E. Carson, John H. Krystal

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)18031-18036
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 16 2014
Externally publishedYes


  • Alcohol dependence
  • GABA receptors
  • Neuroimaging
  • Tobacco smoking
  • Translational

ASJC Scopus subject areas

  • General


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