Amalric M, Berhow M, Polis I, Koob G F
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
Neuropsychopharmacology. 1993 May;8(3):195-200. doi: 10.1038/npp.1993.21.
Operant responses involving a cued discrimination are sensitively disrupted by neuroleptic drugs that block dopamine (DA) receptors in the brain; however, it is not clear which DA receptor subtypes may be involved in these effects. The role of D1 or D2 DA receptor antagonists on the execution of a conditioned reaction-time (RT) motor task was investigated in the present study. Rats were trained to release a lever after the presentation of a visual cue within a RT limit to be reinforced by a food pellet. The D1 receptor antagonist SCH-23390, at doses that significantly decrease the behavioral effects of cocaine, did not impair performance at any dose (5, 10, or 20 micrograms/kg) injected subcutaneously. In contrast, a selective D2 receptor antagonist raclopride (50, 100, or 200 micrograms/kg) induced a dose-dependent increase in the number of incorrect responses (release of the lever over the RT limit) associated with an increase in the RT. The results suggest that the dopaminergic nigrostriatal system, which has previously been shown to be specifically involved in this RT task (Amalric and Koob 1987), appears to be a sensitive site for sensorimotor integration, and that the execution of the conditioned RT motor task may depend preferentially on the activation of the dopaminergic D2 receptors in this system.
涉及线索辨别学习的操作性反应会被阻断大脑中多巴胺(DA)受体的抗精神病药物敏感地破坏;然而,尚不清楚哪些DA受体亚型可能参与这些效应。本研究调查了D1或D2 DA受体拮抗剂在条件反应时(RT)运动任务执行中的作用。训练大鼠在视觉线索出现后,在反应时限制内释放杠杆以获得食物颗粒强化。D1受体拮抗剂SCH-23390,在能显著降低可卡因行为效应的剂量下,皮下注射任何剂量(5、10或20微克/千克)均不损害大鼠的表现。相反,选择性D2受体拮抗剂雷氯必利(50、100或200微克/千克)会导致错误反应(在反应时限制外释放杠杆)数量呈剂量依赖性增加,同时反应时延长。结果表明,先前已证明特定参与此反应时任务的多巴胺能黑质纹状体系统似乎是感觉运动整合的敏感部位,并且条件反应时运动任务的执行可能优先依赖于该系统中多巴胺能D2受体的激活。