Amalric M, Koob G F, Creese I, Swerdlow N R
Life Sci. 1986 Nov 24;39(21):1985-93. doi: 10.1016/0024-3205(86)90322-x.
The dopamine receptor antagonists SCH 23390 and spiperone show highly selective in vitro affinity for D-1 and D-2 dopamine receptor subtypes, respectively. We studied the effects of these selective antagonists on the supersensitive locomotor response to apomorphine in rats following 6- hydroxydopamine (6OHDA) lesions of the nucleus accumbens (N. Acc.). Both D-1 and D-2 receptor antagonists produced dose-dependent blockade of the supersensitive locomotor response at doses that did not depress baseline locomotor activity. The behavioral properties of these D-1 and D-2 receptor antagonists were further examined using a simple step-down motor task. Both antagonists produced catalepsy as evidenced by dose-dependent increases in step- down latency. These results indicate that drugs with distinct in vitro dopamine binding affinities cannot be distinguished on the basis of their ability to inhibit supersensitive locomotor activity or simple motor tasks in rats in vivo.
多巴胺受体拮抗剂SCH 23390和螺哌隆分别对D-1和D-2多巴胺受体亚型表现出高度选择性的体外亲和力。我们研究了这些选择性拮抗剂对伏隔核经6-羟基多巴胺（6OHDA）损伤的大鼠对阿扑吗啡超敏运动反应的影响。D-1和D-2受体拮抗剂在不降低基础运动活性的剂量下均产生了剂量依赖性的超敏运动反应阻断作用。使用简单的阶梯式下降运动任务进一步研究了这些D-1和D-2受体拮抗剂的行为特性。两种拮抗剂均产生了僵住症，阶梯式下降潜伏期的剂量依赖性增加证明了这一点。这些结果表明，具有不同体外多巴胺结合亲和力的药物不能根据其在体内抑制大鼠超敏运动活性或简单运动任务的能力来区分。
