López-Moreno José Antonio, González-Cuevas Gustavo, Navarro Miguel
Department of Psychobiology, Faculty of Psychology, Campus de Somosaguas, Complutense University of Madrid, 28223 Madrid, Spain.
Neurobiol Dis. 2007 Feb;25(2):274-83. doi: 10.1016/j.nbd.2006.09.010. Epub 2006 Oct 24.
Preclinical and clinical research shows that the cannabinoid brain receptor type 1 (CB(1)) modulates alcohol- and nicotine-related behaviors. Throughout the nicotine-induced relapse to alcohol, the rats were pre-treated for 10 days with the CB(1) cannabinoid receptor antagonist rimonabant (0, 0.03, 0.3 and 3.0 mg/kg i.p.). In this condition, a long-lasting nicotine-induced relapse to alcohol was observed, and this effect was reversed in a dose-dependent manner with rimonabant. Surprisingly, rats that were not exposed to nicotine developed tolerance to the effects of rimonabant from the sixth day. Also, 3.0 mg/kg of rimonabant reduced the responses for sucrose. Evaluation in the Elevated Plus-Maze after nicotine treatment did not reveal anxiogenic effects. Finally, at the conclusion of rimonabant treatment, a rapid reinstatement of alcohol consumption was detected. These results suggest that rimonabant can prevent the relapse to alcohol, even when an interaction with nicotine exists-the most frequent situation in human alcohol abuse.
临床前和临床研究表明，大麻素1型脑受体（CB(1)）可调节与酒精和尼古丁相关的行为。在尼古丁诱导的酒精复吸过程中，大鼠连续10天腹腔注射CB(1)大麻素受体拮抗剂利莫那班（剂量分别为0、0.03、0.3和3.0毫克/千克）进行预处理。在此条件下，观察到尼古丁诱导的酒精复吸具有持续性，且利莫那班能以剂量依赖的方式逆转这种效应。令人惊讶的是，未接触尼古丁的大鼠从第6天起对利莫那班的作用产生了耐受性。此外，3.0毫克/千克的利莫那班降低了对蔗糖的反应。尼古丁处理后在高架十字迷宫中的评估未发现致焦虑作用。最后，在利莫那班治疗结束时，检测到酒精摄入量迅速恢复。这些结果表明，即使存在与尼古丁的相互作用（这是人类酒精滥用中最常见的情况），利莫那班仍可预防酒精复吸。
