BRAIN PEPTIDE CELLULAR NEUROBIOLOGY

苯环利定特异性高亲和力结合位点的存在 大脑中的五氯苯酚以及五氯苯酚能在人的大脑中产生深刻的行为 通常类似于精神分裂症精神病的变化要求 应作出重大努力，以确定五氯酚对中枢神经系统的影响 神经系统的过程。中描述的研究的总体目标 这项建议是为了研究苯环利定的作用和最近的一个 分离的PCP样脑肽对体内正常神经生物学过程的影响 大鼠的中枢神经系统。具体地说，多巴胺胞体(A10) 在腹侧被盖区和中边缘-中皮质区域 被这些DA神经元支配的神经元被选作研究对象。这些路径 与解剖和生化底物密切相关 很可能与精神分裂症有关。使用电生理学方法 细胞外单位记录，微离子导入-微压 给药和电刺激选定的通路以 将研究可识别的靶细胞、PCP和PCP样肽，并 比较它们对特定部位和化学模式的选择作用 突触传递的信号。药理操作和选择性 租赁技术将用于区分优先选择的 突触前或突触后的作用部位以及特征 受试化合物与多巴胺能和去甲肾上腺素能的相互作用 系统。最后，我们将确定PCP和PCP样肽神经元 幼稚的动物和长期治疗的动物之间的效果不同 全身注射的五氯苯酚。这里概述的项目应该能够使我们 描述五氯苯酚的部位、机制和功能后果 和PCP样肽在选定的神经元通路上的作用。由此产生的 数据将提供有关PCP独特的基本信息 药理学。反过来，这样的发现可能有助于理解 精神分裂症病因学中涉及的特定化学过程。

The presence of specific high-affinity binding sites for phencyclidine (PCP) in brain and the fact that PCP can produce in man profound behavioral changes often resembling a schizophrenic psychosis requires that substantial efforts be made to determine the effects of PCP on central nervous system processes. The overall goal of the studies described in this proposal is to examine the action of phencyclidine and a recently isolated PCP-like brain peptide on normal neurobiological processes within the rat central nervous system. Specifically, dopamine cell bodies (A10) in the ventral tegmental area and the mesolimbic-mesocortical areas innervated by those DA neurons have been chosen for study. These pathways have been strongly implicated as anatomical and biochemical substrates likely to be involved in schizophrenia. Using electrophysiological methods of extracellular unit recording, microiontophoretic-micropressure administration, and electrical stimulation of selected pathways to identifiable target cells, PCP and the PCP-like peptide will be studied and compared for their selective actions on specific sites and chemical modes of synaptic transmission. Pharmacological manipulations and selective lesioning techniques will be used to discriminate between a preferential presynaptic or postsynaptic site of action as well as to characterize interactions of the test compounds with dopaminergic and noradrenergic systems. Finally, we will determine if PCP and PCP-like peptide neuronal effects differ between naive animals and those chronically treated with systemically administered PCP. The projects outlined here should enable us to characterize the sites, mechanisms and functional consequences of PCP and PCP-like peptide action on selected neuronal pathways. The resulting data will provide essential information concerning PCP's unique pharmacology. In turn, such findings may be useful for the understanding of specific chemical processes involved in the etiology of schizophrenia.