Nicotine Administration in the Cholinergic Basal Forebrain Increases Alcohol Consumption in C57BL/ 6JMice

作者：Sharma Rishi; Sahota Pradeep; Thakkar Mahesh M^*

来源：Alcoholism: Clinical and Experimental Research , 2014, 38(5): 1315-1320.

DOI：10.1111/acer.12353

• Nicotine
• Basal Forebrain
• Microinjection
• Mice
• Alcohol

BackgroundAlcohol 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 42 and 7 subtypes, the most prevalent nAChRs in the brain. Compelling evidence suggests that alcohol enhances the function of 42 subtype. The FDA approved smoking cessation drug, varenicline (Chantix), a partial agonist of 42 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 42 and 7 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.
MethodsUnder 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 2hours daily for 3days. On the fourth day, nicotine or artificial cerebrospinal fluid (ACSF) was microinjected bilaterally in the BF. After 1hour, mice were exposed to alcohol and allowed to self-administer for 4hours. 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.
ResultsAs compared with the ACSF, bilateral nicotine injections into the BF significantly (p<0.05; n=5/group) increased alcohol consumption. Sucrose consumption remained unaffected.
ConclusionsBased on our results, we believe that the BF may have an important role in nicotine-alcohol co-use.

• 出版日期2014-5