Ishiguro H, Iwasaki S, Teasenfitz L, Higuchi S, Horiuchi Y, Saito T, Arinami T, Onaivi E S
Department of Medical Genetics, Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Pharmacogenomics J. 2007 Dec;7(6):380-5. doi: 10.1038/sj.tpj.6500431. Epub 2006 Dec 26.
We tested if cannabinoid type 2 receptor (CB2) in the central nervous system plays a role in alcohol abuse/dependence in animal model and then examined an association between the CB2 gene polymorphism and alcoholism in human. Mice experiencing more alcohol preference by drinking showed reduced Cb2 gene expression, whereas mice with little preference showed no changes of it in ventral midbrain. Alcohol preference in conjunction with chronic mild stress were enhanced in mice treated with CB2 agonist JWH015 when subjected to chronic stress, whereas antagonist AM630 prevented development of alcohol preference. There is an association between the Q63R polymorphism of the CB2 gene and alcoholism in a Japanese population (P=0.007; odds ratio 1.25, 95% CI, (1.06-1.47)). CB2 under such environment is associated with the physiologic effects of alcohol and CB2 antagonists may have potential as therapies for alcoholism.
我们在动物模型中测试了中枢神经系统中的2型大麻素受体（CB2）是否在酒精滥用/依赖中起作用，然后研究了CB2基因多态性与人类酒精中毒之间的关联。通过饮酒表现出更多酒精偏好的小鼠，其腹侧中脑的Cb2基因表达降低，而偏好较低的小鼠则没有变化。在用CB2激动剂JWH015处理的小鼠遭受慢性应激时，酒精偏好与慢性轻度应激相结合的情况会增强，而拮抗剂AM630则可阻止酒精偏好的发展。在日本人群中，CB2基因的Q63R多态性与酒精中毒之间存在关联（P = 0.007；优势比1.25，95%置信区间，（1.06 - 1.47））。在这种环境下，CB2与酒精的生理效应相关，CB2拮抗剂可能具有作为酒精中毒治疗方法的潜力。
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