Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats
Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats
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DOI：
10.1007/s002130100887
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发表时间：
2002-01-01
影响因子：
3.4
通讯作者：
Gessa, GL
中科院分区：
文献类型：
--
作者：
Colombo, G;Serra, S;Gessa, GL
基本原理：最近的研究表明，大麻素CB 1受体拮抗剂，SR 141716，能够减少啮齿类动物的自愿乙醇摄入量，这表明CB 1受体参与神经回路介导的积极的增强性能的乙醇。目的：本研究将大麻素类药物对乙醇摄入的药理学调控研究扩展到激动剂。研究方法：选择性繁殖，撒丁岛酒精偏好（sP）大鼠提供乙醇和水的两瓶自由选择程序下，无限制访问24小时/天。结果如下：WIN 55，212 -2（0.5-2 mg/kg; IP）和CP 55，940（3-30 μ g/kg; IP）急性给药诱导乙醇摄入量显著、剂量依赖性增加。相反，WIN 55，212 -2和CP 55，940处理不影响水消耗量和常规食物和高适口性蔗糖溶液的摄入量。SR 141716（0.3 mg/kg; IP）和阿片受体拮抗剂纳洛酮给药可完全阻止WIN 55，212 -2和CP 55，940对乙醇摄入的刺激作用。(0.1 mg/kg; IP）。结论：给予WIN 55，212 -2和CP 55，940可促进sP大鼠的自愿乙醇摄入。这种作用是由大麻素CB 1受体的刺激介导的，需要内源性阿片系统的激活。本研究的结果进一步支持大麻素CB 1受体是调节乙醇摄入的神经底物的一部分的假设。这些结果还根据WIN 55，212 -2和CP 55，940给药进行了讨论，可能将调节sP大鼠乙醇饮用行为的享乐设定点机制固定到更高水平。
Rationale: Recent studies have shown that the cannabinoid CB1 receptor antagonist, SR 141716, is capable of reducing voluntary ethanol intake in rodents, suggesting the involvement of the CB1 receptor in the neural circuitry mediating the positive reinforcing properties of ethanol. Objectives: The present study extended to the agonists the investigation on the pharmacological manipulation of ethanol intake by cannabinoid agents. Methods: Selectively bred, Sardinian alcohol-preferring (sP) rats were offered ethanol and water under the two-bottle free choice procedure with unlimited access for 24 h/day. Results: The acute administration of WIN 55,212-2 (0.5-2 mg/kg; IP) and CP 55,940 (3-30 mug/kg; IP) induced a significant, dose-dependent increase in ethanol intake. Conversely, water consumption and intake of regular food and a highly palatable sucrose solution were not affected by treatment with WIN 55,212-2 and CP 55,940. The stimulatory effect of WIN 55,212-2 and CP 55,940 on ethanol intake was completely prevented by administration of SR 141716 (0.3 mg/kg; IP) and the opioid receptor antagonist, naloxone. (0.1 mg/kg; IP). Conclusions: Administration of WIN 55,212-2 and CP 55,940 promoted voluntary ethanol intake in sP rats. This effect was mediated by stimulation of the cannabinoid CB1 receptor and required the activation of the endogenous opioid system. The results of the present study add further support to the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate regulating ethanol intake. These results are also discussed in terms of WIN 55,212-2 and CP 55,940 administration possibly fixing to a higher level the hedonic set-point mechanism regulating ethanol drinking behavior in sP rats.