Central administration of an opiate antagonist decreases oral ethanol self-administration in rats
Central administration of an opiate antagonist decreases oral ethanol self-administration in rats
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DOI：
10.1111/j.1530-0277.1999.tb04669.x
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发表时间：
1999-09-01
影响因子：
3.2
通讯作者：
Koob, GF
中科院分区：
文献类型：
--
作者：
Heyser, CJ;Roberts, AJ;Koob, GF
背景资料：阿片肽与酒精的各种行为作用有关，包括其强化作用;然而，这些作用的特定大脑部位的作用仍有待探索。本研究探讨了脑室内（ICV）或脑内注射阿片受体拮抗剂（甲基纳洛铵）对乙醇自我管理的影响。被选为脑内的网站，因为这些地区已被牵连的药物abuse.Methods：雄性Wistar大鼠在有限的访问模式（30分钟/天）响应乙醇（10% w/v）或水在两个杠杆自由选择的条件下使用糖精褪色程序的强化效果。在建立对乙醇的稳定基线反应后，在侧脑室上方立体定向植入动物引导套管或在脑桥核或杏仁核上方植入双侧引导套管。结果：杏仁核内注射甲基纳洛溴铵（0-2000 ng）可显著降低大鼠对乙醇的反应性（250-500 ng）。注射甲基纳洛溴铵到延髓核显着降低乙醇的反应在剂量为500-1000 ng，而更高的剂量需要ICV。结论：这些结果提供了证据，阿片受体位于杏仁核和延髓核可能参与调节乙醇自我管理。
Background: Opioid peptides have been implicated in various behavioral actions of alcohol, including its reinforcing effects; however, the role of specific brain sites for these actions remains to be explored. The present study examined the effects of intracerebroventricular (ICV) or intracerebral injections of an opiate antagonist (methylnaloxonium) on ethanol self-administration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effects of drugs of abuse.Methods: Male Wistar rats were trained in a limited-access paradigm (30 min/day) to respond for ethanol (10% w/v) or water in a two-lever free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, animals were implanted stereotasically with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperative recovery of stable baseline responding, the rats were tested 15 min after ICV or intracerebral microinjections of methylnaloxonium (0-2000 ng).Results: Injections of methylnaloxonium into the amygdala significantly reduced responding for ethanol at doses of 250-500 ng. Injections of methylnaloxonium into the nucleus accumbens significantly reduced responding for ethanol at doses of 500-1000 ng, whereas higher doses were needed ICV.Conclusions: These results provide evidence that opioid receptors located in the amygdala and nucleus accumbens may be involved in the regulation of ethanol self-administration.