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

doi:10.1073/pnas.1413947111

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 journal › Article › peer-review

18 Scopus citations

Abstract

Understanding the effects of tobacco smoking on neuroadaptations in GABA_A 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 GABA_A 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 GABA_A receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABA_A receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABA_A receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABA_A 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 GABA_A receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking.

Original language	English (US)
Pages (from-to)	18031-18036
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	50
DOIs	https://doi.org/10.1073/pnas.1413947111
State	Published - Dec 16 2014
Externally published	Yes

Keywords

Alcohol dependence
GABA receptors
Neuroimaging
Tobacco smoking
Translational

ASJC Scopus subject areas

General

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10.1073/pnas.1413947111

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Cosgrove, K. P., McKay, R., Esterlis, I., Kloczynski, T., Perkins, E., Bois, F., Pittman, B., Lancaster, J., Glahn, D. C., O'Malley, S., Carson, R. E., & Krystal, J. H. (2014). Tobacco smoking interferes with gabaa receptor neuroadaptations during prolonged alcohol withdrawal. Proceedings of the National Academy of Sciences of the United States of America, 111(50), 18031-18036. https://doi.org/10.1073/pnas.1413947111

Cosgrove, KP, McKay, R, Esterlis, I, Kloczynski, T, Perkins, E, Bois, F, Pittman, B, Lancaster, J, Glahn, DC, O'Malley, S, Carson, RE & Krystal, JH 2014, 'Tobacco smoking interferes with gabaa receptor neuroadaptations during prolonged alcohol withdrawal', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 50, pp. 18031-18036. https://doi.org/10.1073/pnas.1413947111

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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.",

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AU - Perkins, Evgenia

AU - Bois, Frederic

AU - Pittman, Brian

AU - Lancaster, Jack

AU - Glahn, David C.

AU - O'Malley, Stephanie

AU - Carson, Richard E.

AU - Krystal, John H.

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N2 - 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.

AB - 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.

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Tobacco smoking interferes with gabaa receptor neuroadaptations during prolonged alcohol withdrawal

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