ACTIVATION OF THE A10 MESOLIMBIC SYSTEM BY THE SIGMA-RECEPTOR AGONIST (+)SKF 10,047 CAN BE BLOCKED BY RIMCAZOLE, A NOVEL PUTATIVE ANTIPSYCHOTIC
ACTIVATION OF THE A10 MESOLIMBIC SYSTEM BY THE SIGMA-RECEPTOR AGONIST (+)SKF 10,047 CAN BE BLOCKED BY RIMCAZOLE, A NOVEL PUTATIVE ANTIPSYCHOTIC
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DOI：
10.1016/0014-2999(88)90362-7
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发表时间：
1988-09-01
影响因子：
5
通讯作者：
FRENCH, ED
中科院分区：
文献类型：
--
作者：
CECI, A;SMITH, M;FRENCH, ED
该研究用电生理学和行为技术评估了新型推定抗精神病药和选择性σ-受体配体，以拮抗σ-受体配体对中皮质边缘多巴胺系统的刺激。激动剂，（+）SKF 10，047。Rimcazole有效地阻断了（+）SKF 10，047诱导的腹侧被盖多巴胺神经元兴奋，而对自发活动或阿朴吗啡诱导的A10放电减慢没有影响。林卡唑还可以对抗（+）SKF 10，047产生的行为多动症，但不能对抗d-苯丙胺产生的行为多动症，d-苯丙胺也是通过相同的中边缘多巴胺途径介导的。这些数据提供了进一步的证据，证明rimcazole的新的药理学特性可能涉及阻断σ-中皮质边缘多巴胺神经元上的受体。
The study evaluated with electrophysiological and behavioral techniques the ability of rimcazole, a novel putative antipsychotic and selective .sigma.-receptor ligand, to antagonize the stimulation of the mesocorticolimbic dopamine system by the .sigma.-agonist, (+)SKF 10,047. Rimcazole effectively blocked the (+)SKF 10,047-induced excitation of ventral tegmental dopamine neurons while having no effect on either spontaneous activity or apomorphine-elicited slowing of A10 firing. Rimcazole also antagonized the behavioral hyperactivity produced by (+)SKF 10,047, but not by d-amphetamine which is also mediated through the same mesolimbic dopamine pathway. These data provide further evidence that rimcazole''s novel pharmacolgic profile may involve a blockade of .sigma.-receptors on mesocorticolimbic dopamine neurons.