EVALUATION OF PCP AND SIGMA EFFECTS ON DA PHYSIOLOGY

滥用药物苯环利定(PCP)对 起源于中脑的多巴胺能(DA)神经元系统。这些 系统被认为与PCP的许多行为影响有关，如 以及它的增强性能和滥用潜力。五氯苯酚将为人所知 阻断DA重摄取，促进DA释放。除了间接DA之外 激动剂作用，PCP作为兴奋性的非竞争性拮抗剂 氨基酸N-甲基-D-天冬氨酸位于一个名为“五氯酚受体”的位置， 也可与氟哌啶醇敏感的西格玛结合部位(“西格玛”)结合 PCP对电生理活动有复杂的影响 黑质纹状体(NS)和中伏隔核(MA)DA细胞。这些影响是 这不仅仅是由于PCP的间接DA激动剂特性。很有可能 PCP在PCP和/或Sigma受体上的作用起重要作用 对DA细胞生理的整体影响。的多重动作 然而，药物排除了对这些贡献的明确评估 不同的受体共同作用于五氯苯酚对DA细胞活性的影响。 最近对五氯苯酚和五氯酚具有选择性的化合物的可获得性 Sigma Sites提供了开始检查的工具 更详细地介绍了五氯苯酚的基本生理和作用机制。 多巴胺神经元的药理学。拟议的体内和体外研究将 使用细胞外单单元记录技术来评估 PCP受体和Sigma受体配体对大鼠DA细胞的影响 活动。这些研究还将探讨可能的行动地点 这些药物对DA细胞活动的影响。体内研究将 检查反向鉴定的NSDA和MADA细胞亚群。这个 滥用五氯苯酚往往涉及重复使用这种药物。这可能是 预计将导致DA细胞自我调节能力的变化 这是由于DA受体的长期间接刺激所致。因此，它的影响 反复服用五氯苯酚对冲动反应的影响- 对躯体树突状DA自体受体的调节将被确定。它是 希望这些研究将使人们更好地了解 PCP对中脑DA神经元的慢性影响。

The drug of abuse, phencyclidine (PCP), has profound effects on dopaminergic (DA) neuronal systems which originate in the midbrain. These systems have been implicated in many of the behavioral effects of PCP as well as its reinforcing properties and abuse potential. PCP is will known to block Da reuptake and enhance DA release. In addition to indirect DA agonist action, PCP acts as a non-competitive antagonist of the excitatory amino acid N-methyl-d-aspartate at a site designated the "PCP receptor," and also interacts with haloperidol-sensitive sigma binding sites ("sigma receptors"). PCP has complex effects on the electrophysiological activity of nigrostriatal (NS) and mesoaccumbens (MA) DA cells. These effects are not due solely to the indirect DA agonist properties of PCP. It is likely that actions of PCP at PCP and/or sigma receptors contribute significantly to its overall effects on DA cell physiology. The multiple actions of the drug, however, have precluded clear assessments of the contributions the separate receptors make to the overall effects of PCP on DA cell activity. The recent availability of compounds which are selective for the PCP and sigma sites has provided tools which are required to begin to examine in greater detail the mechanism of action of PCP on the basal physiology and pharmacology of DA neurons. The proposed in vivo and in vitro studies will employ extracellular single-unit recording techniques in an evaluation of the effects of PCP receptor and sigma receptor ligands onrat DA cell activity. These studies will also look into possible sites of action for the effects of these drugs on DA cell activity. The in vivo studies will examine antidromically identified NSDA and MADA cell subpopulations. The abuse of PCP often involves repeated use os the drug. This might be expected to result in changes in the autoregulatory capacity of DA cells due to prolonged indirect stimulation of DA receptors. Thus, the effects of repeated administration of PCP on the responsiveness of impulse- regulating somatodendritic DA autoreceptors will be determined. It is hoped that these studies will lead to a better understanding of the acute and chronic effects of PCP on midbrain DA neurons.