French E D
Neuropharmacology. 1986 Mar;25(3):241-8. doi: 10.1016/0028-3908(86)90246-7.
Extracellular single unit recordings were used to determine the effects of systemically and iontophoretically applied phencyclidine on electrophysiologically-identified A10 dopamine neurons within the ventral tegmental area of the rat. Intravenous injections of phencyclidine inhibited, as well as excited A10 cells. Approximately 42% of the inhibitions induced by phencyclidine were completely reversed by an injection of haloperidol. The excitatory effects of phencyclidine most often resulted in a state of depolarized inactivation and were not sensitive to haloperidol. The alteration of the activity of A10 cells by systemically-applied phencyclidine was effectively prevented in all animals pretreated with a combination of reserpine and alpha-methyl-p-tyrosine, which depleted stores of central catecholamines by over 90%. In contrast to the data obtained with intravenous injections, iontophoretic applications of phencyclidine produced only inhibition of the activity of the A10 cells and, in a few of these cases the decreased firing rate was accompanied by an increase in the amplitude of the action potential. A comparison of the response patterns of dopaminergic neurons to systemically- and iontophoretically-applied phencyclidine would suggest that excitations induced by phencyclidine are not mediated at the level of the A10 cell bodies but through a site outside the ventral tegmental area. The results of this study also indicate that some of the effects of phencyclidine on the activity of A10 neurons are clearly dependent upon an interaction with dopamine and thus, would support the hypothesis that phencyclidine can act as an indirect dopamine agonist. However, other effects of phencyclidine which are not apparently linked to dopamine may represent the response of a pharmacologically-distinct subpopulation of A10 neurons to phencyclidine.
采用细胞外单单位记录法，以确定全身给药和离子导入法应用苯环利定对大鼠腹侧被盖区经电生理鉴定的A10多巴胺能神经元的影响。静脉注射苯环利定可抑制并兴奋A10细胞。苯环利定诱导的抑制作用中，约42%可被注射氟哌啶醇完全逆转。苯环利定的兴奋作用最常导致去极化失活状态，且对氟哌啶醇不敏感。在所有预先用利血平和α-甲基-对酪氨酸联合处理的动物中，全身应用苯环利定对A10细胞活性的改变均得到有效预防，利血平和α-甲基-对酪氨酸联合处理使中枢儿茶酚胺储备耗竭超过90%。与静脉注射所得数据相反，离子导入法应用苯环利定仅产生对A10细胞活性的抑制作用，在少数情况下，放电频率降低伴随着动作电位幅度增加。比较多巴胺能神经元对全身给药和离子导入法应用苯环利定的反应模式表明，苯环利定诱导的兴奋并非在A10细胞体水平介导，而是通过腹侧被盖区以外的位点介导。本研究结果还表明，苯环利定对A10神经元活性的某些影响显然依赖于与多巴胺的相互作用，因此，支持苯环利定可作为间接多巴胺激动剂的假说。然而，苯环利定的其他明显与多巴胺无关的影响可能代表A10神经元药理学上不同亚群对苯环利定的反应。
