French E D, Mura A, Wang T
Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724.
Synapse. 1993 Feb;13(2):108-16. doi: 10.1002/syn.890130203.
Extracellular single-unit recordings were used to assess the effects of PCP and PCP-like drugs (MK-801 and TCP) on the burst firing of ventral tegmental A10 dopamine neurons in the rat. The effects of these noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists were compared to the potent and competitive NMDA antagonists CGS 19755 and (+/-)CPP, and to BTCP, a PCP-derivative possessing little affinity for the PCP binding site within the ion channel gated by NMDA. PCP, MK-801, and TCP produced dose-dependent increases in the firing rate, which were accompanied by increases in the amount of burst activity, the number of action potentials within a burst, and the conversion of nonbursty cells to bursty. However, the coefficient of variation, a measure of the regularity of firing, was not significantly altered. These predominately excitatory effects contrast with the inhibition of firing, decrease in bursting, and regularization of pattern produced by BTCP. CGS 197555 and (+/-)CPP failed to alter any of the measured parameters. Thus, the increase in firing rate and amount of burst activity of dopamine neurons produced by PCP and PCP-like drugs, and the resultant hyperdopaminergia within the mesolimbic-mesocortical regions, could underlie the psychotomimetic properties of these compounds. Moreover, this effect would not appear to be related to a loss of activity at the NMDA recognition site, as evidenced by the lack of effect of the competitive NMDA antagonists.
采用细胞外单单位记录技术，评估了苯环己哌啶（PCP）及类PCP药物（MK-801和TCP）对大鼠腹侧被盖区A10多巴胺能神经元爆发式放电的影响。将这些非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂的作用，与强效竞争性NMDA拮抗剂CGS 19755和（±）CPP，以及对NMDA门控离子通道内PCP结合位点亲和力极低的PCP衍生物BTCP进行了比较。PCP、MK-801和TCP可使放电频率呈剂量依赖性增加，同时爆发性活动量增加、爆发内动作电位数量增加，且非爆发性细胞转变为爆发性细胞。然而，作为放电规律性指标的变异系数未发生显著改变。这些主要为兴奋性的作用，与BTCP所产生的放电抑制、爆发减少及放电模式规则化形成对比。CGS 19755和（±）CPP未能改变任何测量参数。因此，PCP及类PCP药物所引起的多巴胺能神经元放电频率及爆发性活动量增加，以及中脑边缘-中脑皮质区域内由此产生的多巴胺能亢进，可能是这些化合物拟精神病特性的基础。此外，这种效应似乎与NMDA识别位点活性丧失无关，这一点由竞争性NMDA拮抗剂无作用得以证明。
