Nicotine administration in the cholinergic basal forebrain increases alcohol consumption in C57BL/6J mice

Background: Alcohol and nicotine are the most commonly abused drugs. The frequent co-morbidity of alcohol and nicotine addiction has led to the hypothesis that they may act via a common substrate: the nicotinic acetylcholine receptors (nAChRs) especially α4β2 and α7 subtypes, the most prevalent nAChRs in the brain. Compelling evidence suggests that alcohol enhances the function of α4β2 subtype. The FDA approved smoking cessation drug, varenicline ("Chantix"), a partial agonist of α4β2 nAChR subtype, reduces alcohol self-administration and alcohol craving in humans and rodents. The cholinergic basal forebrain (BF) controls various functions including arousal, attention, and cognition, and there is a predominance of α4β2 and α7 subtypes. We have shown that the BF has an important role in mediating the effects of alcohol and local infusion of nicotine in the BF activates nucleus accumbens. Does BF have any role in mediating the effect of nicotine on alcohol consumption? This study was designed to address this question.

Methods: Under standard surgical procedure, C57BL/6J mice were stereotaxically implanted with bilateral stainless steel guide cannula above the BF. Following post operative recovery and habituation, the animals were exposed to the "drinking-in-the-dark" paradigm whereby alcohol (20%) was presented for 2 hours daily for 3 days. On the fourth day, nicotine or artificial cerebrospinal fluid (ACSF) was microinjected bilaterally in the BF. After 1 hour, mice were exposed to alcohol and allowed to self-administer for 4 hours. The effect of BF nicotine infusion on sucrose consumption was also examined. On completion, mice were euthanized, brain removed and processed to localize the BF injection sites.

Results: As compared with the ACSF, bilateral nicotine injections into the BF significantly (p < 0.05; n = 5/group) increased alcohol consumption. Sucrose consumption remained unaffected.

Conclusions: Based on our results, we believe that the BF may have an important role in nicotine-alcohol co-use.