Steinfels G F, Tam S W, Cook L
E.I. du Pont de Nemours & Co., Inc., Medical Products Department, Wilmington, Delaware 19880-0400.
Neuropsychopharmacology. 1989 Sep;2(3):201-8. doi: 10.1016/0893-133x(89)90023-7.
Extracellular single unit recording techniques were used to study the effects of selective sigma-receptor agonist [(+)-3-PPP, (+)-pentazocine, and DTG] and selective sigma-receptor antagonists (BMY 14802 and Rimcazole) on dopamine neurons of the substantia nigra. Intravenous (IV) administration of sigma agonists decreased, whereas IV administration of the sigma antagonist BMY-14802 increased the firing rate of dopamine neurons. The other sigma antagonist Rimcazole produced inconsistent changes in dopamine unit activity. These data, in conjunction with anatomic data suggesting sigma receptor localization on dopamine neurons in the substantia nigra (Gundlach et al: J Neurosci 6:1757-1770, 1986; Graybiel et al: Soc Neurosci Abstr 13:28, 1987) demonstrate a relationship of the sigma receptor with the dopamine system and further suggest a model system to study agonist-antagonist interactions of sigma ligands. The selective phencyclidine (PCP) agonist MK-801 was equipotent to PCP in regard to stimulatory properties on dopamine neurons. However, the relative potencies do not correspond to their relative binding affinities, suggesting that non-PCP-receptor properties may mediate this effect.
采用细胞外单单位记录技术研究选择性σ受体激动剂[（+）-3-苯基哌嗪、（+）-喷他佐辛和DTG]及选择性σ受体拮抗剂（BMY 14802和利咪唑）对黑质多巴胺能神经元的影响。静脉注射σ受体激动剂可降低多巴胺能神经元的放电频率，而静脉注射σ受体拮抗剂BMY-14802则可增加其放电频率。另一种σ受体拮抗剂利咪唑对多巴胺能神经元活动产生的变化不一致。这些数据，结合提示σ受体定位于黑质多巴胺能神经元的解剖学数据（冈拉克等人：《神经科学杂志》6:1757 - 1770, 1986；格雷比尔等人：《神经科学学会摘要》13:28, 1987），证明了σ受体与多巴胺系统之间的关系，并进一步提示了一个用于研究σ配体激动剂 - 拮抗剂相互作用的模型系统。选择性苯环己哌啶（PCP）激动剂MK - 801在对多巴胺能神经元的刺激特性方面与PCP等效。然而，它们的相对效价与其相对结合亲和力并不对应，这表明非PCP受体特性可能介导了这种效应。
