DOPAMINE NEUROTRANSMISSION AND AMPHETAMINE SENSITIZATION

多巴胺神经传递和安非他明致敏

• 批准号: 2013388
• 负责人: Paul R Vezina
• 金额: $ 19.36万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2013388
• 关键词: amphetamines; behavioral habituation /sensitization; chordate locomotion; cocaine; dopamine; laboratory rat; neural transmission; nucleus accumbens; psychopharmacology

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.

描述：(申请人摘要) 多巴胺神经传递与苯丙胺敏化 脑多巴胺(DA)神经传递的变化被认为与 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发展成 不断增强的反应性或敏感型DA功能。有人建议这样做是为了 导致皮质下DA神经传递异常活跃，并在 随之而来的症状表现。 本申请中提出的实验是继续 研究工作旨在确定哪些神经事件参与了 这种增强在大脑中的发育和行为表达 DA函数。精神运动兴奋剂，如安非他明和可卡因， 增加终末和胞体区DA的胞外水平 中脑边缘多巴胺能神经元，并产生运动激活。重复曝光 这些药物会敏化它们的运动效应，因此随后 再次接触这种药物会产生比以往更大的行为激活 最初是这样。最近的发现表明，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。 拟议中的实验将调查事先接触到 苯丙胺和可卡因对多巴胺突触前和突触后的影响 大鼠伏隔核(NAcc)中脑边缘多巴胺的神经传递 与运动和运动的调解最有牵连的终端场 精神运动兴奋剂的激励作用。因此，这些实验 有三个目标。 目的1.研究敏感化运动和NAcc DA的诱导 对苯丙胺和可卡因的反应是通过评估 他们建议招募兴奋性氨基酸的贡献。目标 2.表征安非他明预合用所引起的变化 中脑边缘多巴胺能神经元可能参与致敏神经元的表达 机动体回应。 目的3.确定安非他明和可卡因是否会产生变化 在突触后，多巴胺和兴奋性氨基酸受体在NAcc 也可能与敏感型运动反应的表达有关。