Varenicline, an α402 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking
Varenicline, an α402 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking
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DOI：
10.1073/pnas.0705368104
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发表时间：
2007-07-24
影响因子：
11.1
通讯作者：
Bartlett, Selena E.
中科院分区：
文献类型：
--
作者：
Steensland, Pia;Simms, Jeffrey A.;Bartlett, Selena E.
酒精依赖是一种影响全世界数百万人的疾病。在酒精依赖者的药物治疗方面取得了一些进展；然而，仍然迫切需要开发新的和额外的治疗方法。酒精和尼古丁通常同时被滥用，有证据表明神经元尼古丁乙酰胆碱受体（nachr）在酒精和尼古丁依赖中都起作用。Varenicline是α 4 β 2 nachr的部分激动剂，可以减少尼古丁的摄入量，最近被批准为戒烟辅助药物。我们研究了伐尼克兰在调节乙醇消耗和寻求使用三种不同的动物饮酒模型中的作用。我们发现，在伐尼克兰治疗前2个月长期暴露于乙醇的动物中，急性给予伐尼克兰的剂量据报道会降低尼古丁奖励，选择性地减少乙醇而不是蔗糖寻求，并减少自愿乙醇而不是水的消耗。此外，长期服用伐尼克兰会降低乙醇消耗量，当不再服用伐尼克兰时，这不会导致乙醇摄入量的反弹增加。这些数据表明，α 4 β 2 nachr可能在长期暴露于乙醇的动物的酒精寻求行为中发挥作用。伐尼克兰在减少乙醇消耗方面的选择性，加上其报道的安全性和对人体的轻微副作用，表明伐尼克兰可能被证明是一种治疗酒精依赖的药物。
Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha 4 beta 2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha 4 beta 2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.