SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats
SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats
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DOI：
10.1097/00008877-200209000-00018
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发表时间：
2002-09-01
影响因子：
1.6
通讯作者：
Soubrié, P
中科院分区：
文献类型：
--
作者：
Cohen, C;Perrault, G;Soubrié, P
最近，中枢 CB1 大麻素受体与大脑奖赏功能有关。在本研究中，我们首先评估了选择性 CB1 受体拮抗剂 SR141716 对尼古丁对大鼠的激励作用的影响。 SR141716（0.3和1mg/kg）的施用减少了尼古丁的自我施用（0.03mg/kg/注射）。 SR141716 (0.3-3 mg/kg) 既不取代尼古丁，也不拮抗尼古丁辨别过程中的尼古丁提示，但在训练辨别 D-苯丙胺的大鼠中，剂量依赖性 (0.01-1 mg/kg) 拮抗尼古丁对 D-苯丙胺的替代。其次，使用脑微透析，SR141716（1-3 mg/kg）阻断尼古丁诱导的伏隔核（NAc）壳和终纹床核中的多巴胺释放。为了研究 SR141716 是否会阻断另一种滥用药物的多巴胺释放作用，我们将神经化学研究扩展到乙醇的作用，SR141716 减少了啮齿动物的乙醇消耗。 SR141716 (3 mg/kg) 也减少了 NAc 中乙醇诱导的多巴胺释放。这些结果表明内源性大麻素系统的激活可能参与尼古丁和乙醇的激励和多巴胺释放作用。因此，如前所述，SR141716 可能有效减少饮酒，并有助于戒烟。 (C) 2002 年利平科特·威廉姆斯·威尔金斯。
The central CB1 cannabinoid receptor has recently been implicated in brain reward function. In the present study we evaluated first the effects of the selective CB1 receptor antagonist, SR141716, on the motivational effects of nicotine in the rat. Administration of SR141716 (0.3 and I mg/kg) decreased nicotine self-administration (0.03 mg/kg/injection). SR141716 (0.3-3 mg/kg) neither substituted for nicotine nor antagonized the nicotine cue in a nicotine discrimination procedure, but dose-dependently (0.01-1 mg/kg) antagonized the substitution of nicotine for D-amphetamine, in rats trained to discriminate D-amphetamine. Secondly, using brain microdialysis, SR141716 (1-3 mg/kg) blocked nicotine-induced dopamine release in the shell of the nucleus accumbens (NAc) and the bed nucleus of the stria terminalis. To investigate whether SR141716 would block the dopamine-releasing effects of another drug of abuse, we extended the neurochemical study to the effect of ethanol, consumption of which in rodents is reduced by SR141716. Dopamine release induced by ethanol in the NAc was also reduced by SR141716 (3 mg/kg). These results suggest that activation of the endogenous cannabinoid system may participate in the motivational and dopamine-releasing effects of nicotine and ethanol. Thus, SR141716 may be effective in reduction of alcohol consumption, as previously suggested, and as an aid for smoking cessation. (C) 2002 Lippincott Williams Wilkins.