Persistent behavioural effect of apomorphine in 6-hydroxydopamine-lesioned rats
Persistent behavioural effect of apomorphine in 6-hydroxydopamine-lesioned rats
复制标题
阿朴吗啡对 6-羟基多巴胺损伤大鼠的持续行为影响
作者：
P. B. Silverman;B. Ho
单侧黑质纹状体损伤的啮齿动物的旋转（盘旋）行为已被广泛用于研究黑质纹状体功能和多巴胺能化合物的作用1。通过单侧显微注射儿茶酚胺能神经毒素 6-羟基多巴胺 (6-OHDA) 损伤的大鼠会自发地表现出轻微的同侧（朝向损伤侧）旋转。多巴胺受体激动剂阿朴吗啡的全身攻击会诱导对侧主动旋转，这显然是由于受损半球的超敏感性所致2,3。我们在此报告，阿朴吗啡治疗还会导致自发（未用药）旋转的异常持久的变化。在用每公斤 50 微克阿朴吗啡治疗一次后，暴露于旋转环境导致对侧旋转的短暂而强烈的爆发。这种行为在药物治疗后数月内很明显，直到治疗后两周才完全形成，并且在病变但未接受过药物治疗的大鼠中从未观察到。与急性效应不同，潜在的阿扑吗啡效应与测试范围内的剂量成反比。这种行为对于药物治疗发生的环境来说是相对特定的，这表明学习的作用，但很难用这种解释来协调逆剂量反应函数、缺乏新近效应以及无法使用(+)苯丙胺诱导类似现象。
The rotational (circling) behaviour of rodents with unilateral nigrostriatal damage has been used extensively to investigate nigrostriatal function and the action of dopaminergic compounds1. Rats lesioned by unilateral microinjection of the catecholaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), spontaneously exhibit slight ipsilateral (towards the lesioned side) rotation. Systemic challenge with the dopamine receptor agonist apomorphine induces active contralateral rotation, apparently as a result of supersensitivity in the lesioned hemisphere2,3. We report here that apomorphine treatment also results in an extraordinarily persistent change in spontaneous (undrugged) rotation. After one treatment with 50 µg per kg apomorphine, exposure to the rotation environment resulted in a brief, intense burst of contralateral rotation. This behaviour, apparent for months after drug treatment, did not fully develop until 2 weeks after treatment and was never observed in lesioned, but otherwise drug-naive rats. The latent apomorphine effect, unlike the acute effect, was inversely related to dose over the range tested. The behaviour was relatively specific for the environment in which drug treatment had occurred, suggesting a role for learning, but it is difficult to reconcile the inverse dose–response function, lack of recency effect and inability to induce an analogous phenomenon using (+)amphetamine with this explanation.