Grupo de Neurociencias, Laboratorio de Canabinoides, Depto. de Fisiología, Universidad Nacional Autónoma de México, Apdo. Postal 70-250, México, D.F. 04510, Mexico.
Brain Res Bull. 2013 Feb;91:31-7. doi: 10.1016/j.brainresbull.2012.11.010. Epub 2013 Jan 2.
Alcohol use disorder is a compulsive behavior driven by motivational systems and by a poor control of consummatory behavior. The entopeduncular nucleus (EP) seems to be involved in the regulation of executive mechanisms, hence, in the expression of behavior. Endocannabinoids (eCB) are involved in alcohol intake mechanisms. The eCB receptor name cannabinoid receptor 1 (CB1R) is expressed in the EP in GABAergic terminals. The role of the eCB system (eCBs) of the EP in the modulation of alcohol seeking and intake behavior is unknown. Therefore, we decided to investigate the role of the eCBs and its interaction with GABA transmission in rat EP, in the regulation of alcohol intake behavior. Rats were submitted to a 10-day period of moderate alcohol (10% in tap water) ingestion. No tap water was available. On day 11, either anandamide (AEA, CB1 receptor agonist), AM251 (CB1R inverse agonist), baclofen (BAC, GABAB receptor agonist), or CGP35348 (GABAB receptor antagonist) was administered into the EP. One bottle of water and one of alcohol (10% in water) were available ad libitum for the following 24 h, and consumption was quantified at the end of this period. Results show that administration of AEA into the EP decreased alcohol consumption while AM251 and BAC administered independently increased alcohol consumption. AEA prevented the increase induced by AM251 or BAC. Likewise, CGP35348 prevented alcohol ingestion induced by AM251. These data suggest that eCBs dysfunction in the EP may be playing a crucial role in the abuse and dependence of alcohol and other drugs.
酒精使用障碍是一种由动机系统驱动的强迫行为，以及对消费行为的控制能力差。脚桥核（EP）似乎参与了执行机制的调节，因此，参与了行为的表达。内源性大麻素（eCB）参与了酒精摄入机制。内源性大麻素受体 1（CB1R）的名称在 EP 中的 GABA 能末梢中表达。EP 中 eCB 系统（eCBs）在调节酒精寻求和摄入行为中的作用尚不清楚。因此，我们决定研究 EP 中 eCB 及其与 GABA 传递的相互作用在调节酒精摄入行为中的作用。大鼠被给予 10 天的中等酒精（自来水中的 10%）摄入。没有自来水可用。在第 11 天，将大麻素（AEA，CB1 受体激动剂）、AM251（CB1R 反向激动剂）、巴氯芬（BAC，GABAB 受体激动剂）或 CGP35348（GABAB 受体拮抗剂）注入 EP。1 瓶水和 1 瓶酒精（10%的水）可供自由饮用 24 小时，在此期间结束时定量消耗。结果表明，AEA 注入 EP 可减少酒精消耗，而 AM251 和 BAC 单独给药可增加酒精消耗。AEA 可防止 AM251 或 BAC 引起的增加。同样，CGP35348 可防止 AM251 诱导的酒精摄入。这些数据表明，EP 中的 eCB 功能障碍可能在酒精和其他药物的滥用和依赖中起着至关重要的作用。
