Department of Psychiatry, School of Medicine, Yale University, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA.
Psychopharmacology (Berl). 2010 Mar;208(4):613-26. doi: 10.1007/s00213-009-1759-1.
Alcohol and nicotine are commonly co-abused. Genetic correlations between responses to these drugs have been reported, providing evidence that common genes underlie the response to alcohol and nicotine. Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system are important in mediating nicotine response, and several studies suggest that alcohol may also interact with these nAChRs.
The aim of this study was to examine the role of nAChRs containing α7 or β2 subunits in ethanol consumption.
A two-bottle choice paradigm was used to determine ethanol consumption in wild-type and nAChR subunit knockout mice. Challenge studies were performed using the α4β2 nAChR partial agonist varenicline.
Mice lacking the β2 subunit consumed a similar amount of ethanol compared to their wild-type siblings in an ethanol-drinking paradigm. In contrast, mice lacking the α7 nAChR receptor subunit consumed significantly less ethanol than wild-type mice but consumed comparable amounts of water, saccharin, and quinine. In C57BL/6J mice, varenicline dose-dependently decreased ethanol consumption with a significant effect of 2 mg/kg, without affecting water or saccharin consumption. This effect of varenicline was not reversed in mice lacking either the α7 or β2 subunit, providing evidence that nAChRs containing one of these subunits are not required for this effect of varenicline.
This study provides evidence that α7 nAChRs are involved in ethanol consumption and supports the idea that pharmacological manipulation of nAChRs reduces ethanol intake. Additional nAChRs may also be involved in ethanol intake, and there may be functional redundancy in the nicotinic control of alcohol drinking.
酒精和尼古丁通常是共同滥用的。人们已经报道了对这些药物反应的遗传相关性，这为酒精和尼古丁反应的共同基因提供了证据。中脑边缘多巴胺系统中的烟碱型乙酰胆碱受体（nAChRs）在介导尼古丁反应中很重要，有几项研究表明，酒精也可能与这些 nAChRs 相互作用。
本研究旨在研究含有α7 或β2 亚基的 nAChRs 在乙醇消耗中的作用。
使用双瓶选择范式来确定野生型和 nAChR 亚基敲除小鼠中的乙醇消耗。使用α4β2 nAChR 部分激动剂伐伦克林进行挑战研究。
与野生型兄弟姐妹相比，缺乏β2 亚基的小鼠在乙醇饮用范式中消耗的乙醇量相似。相比之下，缺乏α7 nAChR 受体亚基的小鼠消耗的乙醇量明显少于野生型小鼠，但消耗的水量、糖精和奎宁相当。在 C57BL/6J 小鼠中，伐伦克林剂量依赖性地降低乙醇消耗，2mg/kg 的剂量有显著效果，而不影响水或糖精的消耗。缺乏α7 或β2 亚基的小鼠中伐伦克林的这种作用没有逆转，这表明含有这些亚基之一的 nAChRs 不是伐伦克林这种作用所必需的。
本研究提供了证据表明α7 nAChRs 参与了乙醇消耗，并支持了药理学操纵 nAChRs 可减少乙醇摄入的观点。其他 nAChRs 也可能参与乙醇摄入，而尼古丁对酒精摄入的控制可能存在功能冗余。
