French E D, Ceci A
Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724.
Neurosci Lett. 1990 Nov 13;119(2):159-62. doi: 10.1016/0304-3940(90)90823-r.
The response of ventral tegmental (VTA) A10 dopamine neurons to a series of compounds covering the spectrum from high-affinity phencyclidine receptor ligands (MK-801, PCP) to high-affinity sigma-receptor ligands [+)-pentazocine, DTG) was measured using single-unit extracellular recording techniques in the rat. Dose-response comparisons revealed that MK-801 was 3, 6, 19 and 119 times more potent at activating A10 neurons than PCP, (+)-SKF-10,047, ketamine and (+)-pentazocine, respectively. DTG (1,3-di-o-tolylguanidine), the most selective sigma-ligand, and U50,488H, a kappa-opiate, failed to produce any stimulation of firing. Also, pretreatment with haloperidol, a potent sigma-receptor ligand, did not prevent MK-801-induced excitations. Thus, the activation of the A10-mesolimbic-mesocortical dopamine pathways by PCP, PCP-like drugs and sigma-psychotomimetics is mediated by the PCP receptor, not the haloperidol-sensitive sigma-receptor, with potencies directly correlated to their activity as non-competitive N-methyl-D-aspartate (NMDA) antagonists.
采用大鼠单单位细胞外记录技术，测量腹侧被盖区（VTA）A10多巴胺能神经元对一系列化合物的反应，这些化合物涵盖了从高亲和力苯环利定受体配体（MK-801、苯环利定）到高亲和力σ受体配体[（+）-喷他佐辛、DTG]的范围。剂量反应比较显示，MK-801激活A10神经元的效力分别比苯环利定、（+）-SKF-10,047、氯胺酮和（+）-喷他佐辛强3倍、6倍、19倍和119倍。最具选择性的σ配体DTG（1,3-二邻甲苯基胍）和κ阿片类药物U50,488H未能引起任何放电刺激。此外，用强效σ受体配体氟哌啶醇预处理并不能阻止MK-801引起的兴奋。因此，苯环利定、类苯环利定药物和σ拟精神病药物对A10-中脑边缘-中脑皮质多巴胺通路的激活是由苯环利定受体介导的，而非氟哌啶醇敏感的σ受体，其效力与它们作为非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂的活性直接相关。
