MOTOR EFFECTS OF 2 SIGMA LIGANDS MEDIATED BY NIGROSTRIATAL DOPAMINE NEURONS
MOTOR EFFECTS OF 2 SIGMA LIGANDS MEDIATED BY NIGROSTRIATAL DOPAMINE NEURONS
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DOI：
10.1002/syn.890040311
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发表时间：
1989-01-01
期刊：
影响因子：
2.3
通讯作者：
WALKER, JM
中科院分区：
文献类型：
--
作者：
GOLDSTEIN, SR;MATSUMOTO, RR;WALKER, JM
(+)-Pentazocine 是一种对 PCP 受体缺乏亲和力的有效 sigma 配体，在大鼠黑质中显微注射后产生剂量依赖性对侧循环行为。这种效应因上行多巴胺神经元的 6-羟基多巴胺 (6-OHDA) 损伤而减弱，并因全身注射安非他明而增强。 6-OHDA 损伤还减弱了另一种选择性 σ 配体 1,3-二邻甲苯胍 (DTG) 产生的循环。这些发现表明西格玛受体参与运动的神经控制和上行多巴胺系统的调节。由于测试的所有典型抗精神病药物均以小于1μM的Ki值与σ受体结合，因此这些发现进一步表明σ受体可能介导抗精神病药物治疗的一些运动副作用。
(+)-Pentazocine, a potent sigma ligand that lacks affinity for PCP receptors, produced dose-dependent contralateral circling behavior following microinjections in the substantia nigra of rats. This effect was attenuated by 6-hydroxydopamine (6-OHDA) lesions of ascending dopamine neurons and enhanced by systemic injections of amphetamine. 6-OHDA lesions also attenuated the circling produced by another selective sigma ligand, 1,3-di-o-tolylguanidine (DTG). These findings suggest that sigma receptors are involved in the neural control of movement and the regulation of the ascending dopamine system. Since all typical antipsychotic drugs tested bind to sigma receptors with Ki values less than 1 .mu.M, these findings further suggest that sigma receptors may mediate some of the motor side effects of antipsychotic drug therapy.