Nicotine administration in the cholinergic basal forebrain increases alcohol consumption in C57BL/6J mice.
Nicotine administration in the cholinergic basal forebrain increases alcohol consumption in C57BL/6J mice.
复制标题
在胆碱能基底前脑中施用尼古丁会增加 C57BL/6J 小鼠的酒精消耗量。
DOI：
10.1111/acer.12353
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Thakkar,MaheshM
中科院分区：
文献类型：
--
作者：
Sharma,Rishi;Sahota,Pradeep;Thakkar,MaheshM
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) especiallyα4β2 andα7 subtypes, the most prevalent nAChRs in the brain. Compelling evidence suggests that alcohol enhances the function ofα4β2 subtype. The FDA approved smoking cessation drug, varenicline (“Chantix”), a partial agonist ofα4β2 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 ofα4β2 andα7 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 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.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.
