Cannabinoid-1 receptor neutral antagonist reduces binge-like alcohol consumption and alcohol-induced accumbal dopaminergic signaling.
Cannabinoid-1 receptor neutral antagonist reduces binge-like alcohol consumption and alcohol-induced accumbal dopaminergic signaling.
复制标题
DOI：
10.1016/j.neuropharm.2017.10.040
复制
发表时间：
2018-03-15
影响因子：
4.7
通讯作者：
Vinod KY
中科院分区：
文献类型：
--
作者：
Balla A;Dong B;Shilpa BM;Vemuri K;Makriyannis A;Pandey SC;Sershen H;Suckow RF;Vinod KY
酗酒（乙醇）饮酒与对我们的健康和社会的严重不良影响有关。利莫那班（SR 141716 A）是一种CB 1受体反向激动剂，先前已证明对尼古丁戒断和肥胖有效。然而，使用利莫那班的研究被终止，因为它与抑郁和焦虑的风险增加有关。在本研究中，我们研究了AM4113，一种新的CB 1受体中性拮抗剂对酗酒样乙醇饮用C57 BL/6 J小鼠的药代动力学和影响，使用两瓶选择饮用黑暗（DID）的范例。结果表明，AM4113在脑中的消除比在血浆中慢。AM4113抑制乙醇消耗和偏好，而对体重、步行活动、促味剂（糖精和奎宁）偏好和乙醇代谢无显著影响。AM4113预处理减少乙醇诱导的多巴胺释放的增加。总的来说，这些数据表明，CB 1受体介导的调控酗酒样乙醇消耗和中脑边缘多巴胺能信号传导的重要作用，并进一步指出CB 1中性拮抗剂治疗酗酒乙醇饮用的潜在效用。
Binge alcohol (ethanol) drinking is associated with profound adverse effects on our health and society. Rimonabant (SR141716A), a CB1 receptor inverse agonist, was previously shown to be effective for nicotine cessation and obesity. However, studies using rimonabant were discontinued as it was associated with an increased risk of depression and anxiety. In the present study, we examined the pharmacokinetics and effects of AM4113, a novel CB1 receptor neutral antagonist on binge-like ethanol drinking in C57BL/6J mice using a two-bottle choice drinking-in-dark (DID) paradigm. The results indicated a slower elimination of AM4113 in the brain than in plasma. AM4113 suppressed ethanol consumption and preference without having significant effects on body weight, ambulatory activity, preference for tastants (saccharin and quinine) and ethanol metabolism. AM4113 pretreatment reduced ethanol-induced increase in dopamine release in nucleus accumbens. Collectively, these data suggest an important role of CB1 receptor-mediated regulation of binge-like ethanol consumption and mesolimbic dopaminergic signaling, and further points to the potential utility of CB1 neutral antagonists for the treatment of binge ethanol drinking.
登录
查看更多内容
影响因子：
7.6
作者：
Hansson, Anita C.;Bermudez-Silvaz, Francisco J.;Heilig, Markus
通讯作者：
Heilig, Markus
影响因子：
7.6
作者：
Blednov, Yuri A.;Cravatt, Benjamin F.;Harris, R. Adron
通讯作者：
Harris, R. Adron
影响因子：
4.8
作者：
Gueye, Aliou B.;Pryslawsky, Yaroslaw;Le Foll, Bernard
通讯作者：
Le Foll, Bernard
影响因子：
3.6
作者：
Colombo, G;Serra, S;Gessa, GL
通讯作者：
Gessa, GL
影响因子：
5.3
作者：
Caille, Stephanie;Alvarez-Jaimes, Lily;Parsons, Loren H.
通讯作者：
Parsons, Loren H.