Alesdatter J.E., Kalivas P.W.
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA.
Behav Pharmacol. 1993 Dec;4(6):645-651.
Microinjection of the mu opioid, [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) into the ventral pallidum (VP) elicits a motor stimulant response. The coadministration of dopamine (DA) antagonists with DAMGO into the VP was used to determine the role of DA transmission in the motor response. The mixed D1/D2 antagonist, fluphenazine, was found to produce a partial reduction in DAMGO-induced motor activity. To evaluate the role of DA receptor subtypes, the D1 and D2 selective antagonists, SCH-23390 and raclopride, respectively, were coadministered with DAMGO into the VP. SCH-23390 was found to produce a dose-dependent reduction in both horizontal and vertical motor activity with a minimum effective dose of 0.3nmol/side. However, only a partial reduction in horizontal activity occurred with a dose of SCH-23390 as high as 6.0nmol/side. Raclopride was without effect at any dose examined, and an equimolar mixture of SCH-23390 and raclopride did not alter the minimum effective dose nor the maximum reduction in motor activity produced by SCH-23390 alone. It is concluded that stimulation of D1 receptors is permissive to the motor stimulant effect elicited by DAMGO in the VP.
将μ阿片类药物[D - Ala(2), N - Me - Phe(4), Gly - ol(5)] - 脑啡肽(DAMGO)微量注射到腹侧苍白球(VP)会引发运动兴奋反应。将多巴胺(DA)拮抗剂与DAMGO共同注射到VP中,以确定DA传递在运动反应中的作用。发现混合的D1/D2拮抗剂氟奋乃静可使DAMGO诱导的运动活动部分降低。为了评估DA受体亚型的作用,分别将D1和D2选择性拮抗剂SCH - 23390和雷氯必利与DAMGO共同注射到VP中。发现SCH - 23390可使水平和垂直运动活动产生剂量依赖性降低,最小有效剂量为0.3nmol/侧。然而,当SCH - 23390剂量高达6.0nmol/侧时,仅水平活动出现部分降低。雷氯必利在任何检测剂量下均无作用,且SCH - 23390和雷氯必利的等摩尔混合物既未改变最小有效剂量,也未改变单独使用SCH - 23390时产生的最大运动活动降低程度。结论是,刺激D1受体允许DAMGO在VP中引发运动兴奋效应。