Racz Ildiko, Bilkei-Gorzo Andras, Toth Zsuzsanna E, Michel Kerstin, Palkovits Miklós, Zimmer Andreas
Laboratory of Molecular Neurobiology, Department of Psychiatry, University of Bonn, 53105 Bonn, Germany.
J Neurosci. 2003 Mar 15;23(6):2453-8. doi: 10.1523/JNEUROSCI.23-06-02453.2003.
Although many people drink alcohol regularly, only some become addicted. Several studies have shown that genetic and environmental factors contribute to individual differences in the vulnerability to the effects of alcohol (Nestler, 2000; Kreek, 2001; Crabbe, 2002). Among the environmental factors, stress is perhaps the most important trigger for relapse after a period of abstinence (Koob and Nestler, 1997; Piazza and Le Moal, 1998; Koob and Le Moal, 2001; Weiss et al., 2001). Here we show that ethanol withdrawal symptoms were completely absent in cannabinoid CB1 receptor-deficient mice, although acute effects of ethanol and ethanol tolerance and preference were basically normal. Furthermore, foot-shock stress had no affect on alcohol preference in Cnr1-/- mice, although it induced a dramatic increase in Cnr1+/+ animals. These results reveal a critical role for the CB1 receptor in clinically important aspects of alcohol dependence and provide a rationale for the use of CB1 receptor antagonists in the treatment of alcohol addiction.
虽然许多人经常饮酒，但只有一部分人会上瘾。多项研究表明，遗传和环境因素导致个体对酒精影响的易感性存在差异（内斯特勒，2000年；克里克，2001年；克拉布，2002年）。在环境因素中，压力可能是禁欲一段时间后复发的最重要诱因（库布和内斯特勒，1997年；皮亚扎和勒莫阿尔，1998年；库布和勒莫阿尔，2001年；韦斯等人，2001年）。我们在此表明，大麻素CB1受体缺陷型小鼠完全没有出现乙醇戒断症状，尽管乙醇的急性效应、乙醇耐受性和偏好基本正常。此外，足部电击应激对Cnr1-/-小鼠的酒精偏好没有影响，尽管它在Cnr1+/+动物中引起了显著增加。这些结果揭示了CB1受体在酒精依赖的临床重要方面的关键作用，并为使用CB1受体拮抗剂治疗酒精成瘾提供了理论依据。
