DOPAMINE NEUROTRANSMISSION AND AMPHETAMINE SENSITIZATION

描述：（申请人摘要） 多巴胺的神经传递与安非他明的增敏作用 大脑多巴胺（DA）神经传递的变化与 包括精神分裂症和药物滥用在内的几种疾病过程。一 这两种疾病共同的变化是 增加反应性或敏感性DA功能。有人建议， 导致皮质下DA神经传递异常活跃， 随之而来的表达。 本申请中提出的实验是一个持续的实验的一部分。 研究工作旨在确定哪些神经活动参与了 发展和这种增强在大脑中的行为表达 DA函数。精神刺激药物，如安非他明和可卡因， 增加DA的细胞外水平在终端和细胞体区域 中脑边缘DA神经元并产生运动激活。反复暴露 对这些药物的敏感性使它们的运动效应， 再次暴露于药物会产生更大的行为激活， 一开始最近的研究结果表明，中脑DA的变化， 神经传递可能对诱导和 这种行为敏感化的表现。 所提出的实验将调查先前暴露于 苯丙胺和可卡因对DA突触前和突触后方面的影响 神经传递在大鼠延髓核（NAcc），中脑边缘DA 终端领域最涉及调解的运动和 精神兴奋剂的激励作用。因此，实验 有三个目标。 AIM 1.研究诱导致敏运动和NAcc DA 安非他明和可卡因的反应是通过评估 他们建议的兴奋性氨基酸的募集的贡献。目的 2.为了表征安非他明在突触前产生的变化， 中脑边缘DA神经元可能有助于表达致敏的 运动反应。 AIM 3.以确定安非他明和可卡因是否产生变化 突触后多巴胺和兴奋性氨基酸受体的NAcc， 也可能有助于敏化运动反应的表达。

DESCRIPTION: (Applicant's Abstract) DOPAMINE NEUROTRANSMISSION AND AMPHETAMINE SENSITIZATION Changes in brain dopamine (DA) neurotransmission have been implicated in several disease processes including schizophrenia and substance abuse. One change posited to be common to both these disorders is the development of increasingly reactive or sensitized DA function. This has been suggested to result in unusually active levels of subcortical DA neurotransmission and in the ensuing expression of symptomatology. The experiments proposed in this application are part of a continuing research effort aimed at determining what neural events are involved in the development and in the behavioral expression of such enhancements in brain DA function. Psychomotor stimulant drugs, such as amphetamine and cocaine, increase extracellular levels of DA in the terminal and cell body regions of mesolimbic DA neurons and produce locomotor activation. Repeated exposure to these drugs sensitizes their locomotor effects so that subsequent reexposure to the drug produces greater behavioral activation than seen initially. Recent findings suggest that changes in midbrain DA neurotransmission may contribute importantly to both the induction and expression of this behavioral sensitization. The experiments proposed will investigate the effect of prior exposure to amphetamine and cocaine on pre- and postsynaptic aspects of DA neurotransmission in the rat nucleus accumbens (NAcc), the mesolimbic DA terminal field most implicated in mediation of the locomotor and motivational effects of psychomotor stimulants. As such, the experiments have three aims. AIM 1. To investigate how INDUCTION of sensitized locomotor and NAcc DA responding by amphetamine and cocaine is produced by assessing the contribution of their suggested recruitment of excitatory amino acids. AIM 2. To characterize the changes produced by amphetamine PRESYNAPTICALLY in mesolimbic DA neurons that may contribute to the EXPRESSION of sensitized locomotor responding. AIM 3. To determine whether amphetamine and cocaine produce changes POSTSYNAPTICALLY in DA and excitatory amino acid receptors in the NAcc that may also contribute to the EXPRESSION of sensitized locomotor responding.