Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans
Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans
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DOI：
10.1038/sj.tpj.6500431
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发表时间：
2007-12-01
影响因子：
2.8
通讯作者：
Onaivi, E. S.
中科院分区：
文献类型：
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作者：
Ishiguro, H.;Iwasaki, S.;Onaivi, E. S.
我们在动物模型中检测了中枢神经系统中的大麻素2型受体(CB2)在酒精滥用/依赖中的作用，然后考察了CB2基因多态性与人类酒精中毒的关系。饮酒偏好较高的小鼠，CB2基因表达降低，而饮酒偏好较小的小鼠，腹侧中脑CB2基因表达没有变化。在慢性应激下，CB2激动剂JWH015处理的小鼠的酒精偏好与慢性轻度应激相结合，而拮抗剂AM630则阻止了酒精偏好的发展。在日本人群中，Cb2基因Q63R多态与酒精中毒有关联(P=0.007；优势比1.25，95%CI，(1.06~1.47))。在这种环境下，CB2与酒精的生理效应有关，CB2拮抗剂可能具有治疗酒精中毒的潜力。
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% Cl, (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.