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向大鼠终纹床核背外侧注射多巴胺D-1受体拮抗剂SCH 23390可降低可卡因的强化作用。

The dopamine D-1 receptor antagonist SCH 23390 injected into the dorsolateral bed nucleus of the stria terminalis decreased cocaine reinforcement in the rat.

作者信息

Epping-Jordan M P, Markou A, Koob G F

机构信息

Department of Neuropharmacology, Division of Psychopharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Brain Res. 1998 Feb 16;784(1-2):105-15. doi: 10.1016/s0006-8993(97)01190-6.

Abstract

The effects of bilateral intracranial injections of the D-1 dopamine receptor antagonist SCH 23390 HCl (0, 0.8, 1.6, 3.2, and 6.4 microgram total bilateral dose) administered into the dorsolateral bed nucleus of the stria terminalis (dlBNST) immediately prior to a 3 h intravenous cocaine self-administration session were examined. In addition, anatomical control injections of the most effective dose of SCH 23390 HCl (6.4 micogram) were made either 1.5 mm dorsal to the dlBNST or into the lateral ventricle. Injections directly into the dlBNST, but not those dorsal to the dlBNST or into the lateral ventricle, significantly increased the rate of cocaine self-administration within the first 20 min of the self-administration session, consistent with a partial attenuation of the reinforcing effects of cocaine under a fixed-ratio schedule of reinforcement (0.25 mg cocaine iv; fixed-ratio 5, timeout 20 s). Injections into all three sites increased cocaine self-administration across the entire 3 h session. These results suggest a role for D-1 dopamine receptors in the dlBNST in the reinforcing properties of self-administered cocaine, and also support the hypothesis that D-1 dopamine receptors in the 'extended amygdala' may play a significant role in cocaine self-administration.

摘要

在3小时静脉注射可卡因自我给药实验前,立即向终纹床核背外侧(dlBNST)双侧颅内注射D-1多巴胺受体拮抗剂盐酸SCH 23390(双侧总剂量0、0.8、1.6、3.2和6.4微克),观察其效果。此外,在dlBNST背侧1.5毫米处或侧脑室内进行最有效剂量盐酸SCH 23390(6.4微克)的解剖学对照注射。直接注射到dlBNST内,但不是dlBNST背侧或侧脑室内的注射,在自我给药实验的前20分钟内显著增加了可卡因自我给药的速率,这与在固定比率强化程序(0.25毫克静脉注射可卡因;固定比率5,超时20秒)下可卡因强化作用的部分减弱一致。在整个3小时实验中,向所有三个部位的注射均增加了可卡因的自我给药。这些结果表明,dlBNST中的D-1多巴胺受体在自我给药可卡因的强化特性中起作用,也支持了“扩展杏仁核”中的D-1多巴胺受体可能在可卡因自我给药中起重要作用的假说。

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