Nicotine and Nicotine Abstinence Do Not Interfere with GABAA Receptor Neuroadaptations During Alcohol Abstinence

BackgroundAlcohol dependence and tobacco smoking are highly comorbid, and treating both conditions simultaneously is controversial. Previously, we showed that tobacco smoking interferes with GABA(A) receptor neuroadaptations during alcohol withdrawal in humans, while this effect did not occur with continued nicotine use during alcohol abstinence in nonhuman primates. Here, we extend our previous work by measuring GABA(A) receptor availability with positron emission tomography (PET) during drug abstinence in nonhuman primates exposed to alcohol alone, nicotine and alcohol together, and alcohol abstinence with continued nicotine exposure. MethodsTwenty-four adolescent male rhesus macaques orally self-administered alcohol and nicotine, available separately in water and saccharin, over 20weeks. The groups included alcohol alone (n=8); nicotine and alcohol with simultaneous abstinence (n=8); nicotine and alcohol with alcohol abstinence while nicotine was still available (n=8); and a pilot group of animals consuming nicotine alone (n=6). Animals were imaged with [C-11]flumazenil PET to measure binding potential (BPND), an index of GABA(A) receptor availability. Imaging occurred at baseline (drug-naive), and following alcohol and/or nicotine cessation at 1day, 8days, and 12weeks of abstinence. Generalized linear mixed models were used to examine the time course of [C-11]flumazenil BPND during alcohol abstinence across groups. ResultsAnimals consumed 3.951.22g/kg/d alcohol and 55.4 +/- 35.1mg/kg/d nicotine. No significant group effects were observed in [C-11]flumazenil BPND during alcohol abstinence; however, a main effect of time was detected. Post hoc analyses indicated that all groups abstaining from alcohol exhibited significantly increased GABA(A) receptor availability at 1day and 8days (but not 12weeks) of abstinence relative to baseline, while no changes in [C-11]flumazenil BPND during nicotine abstinence alone were observed. ConclusionsThese data indicate that neither nicotine nor nicotine abstinence interferes with GABA(A) receptor neuroadaptations during alcohol withdrawal. This conclusion is consistent with our previous study and does not contradict the use of nicotine replacement therapies or non-nicotinic-acting pharmaceuticals to quit smoking during alcohol withdrawal from a GABAergic perspective.