MECHANISMS OF ACTION OF DRUGS OF ABUSE--AMPHETAMINE

该申请寻求延长五年的研究支持 研究精神病的作用部位和机制 兴奋剂，包括安非他明和可卡因。 实验 被提议来确定改变的潜在机制 在儿茶酚胺能和非儿茶酚胺能神经元末梢中 兴奋性，包括分析可卡因对 儿茶酚胺能末梢兴奋性和是否改变 大鼠脑内多巴胺能神经元的终末兴奋性 发生在长期植入的行为动物身上。 试图 将收集有关身份的证据 和多巴胺能突触的突触后靶点， 并评估多巴胺能突触的关系 新纹状体中产生的信号， 多巴胺能岛或纹状体和基质区室。 建议进一步的实验来评估 安非他明给药对新生纹状体神经元活动的影响 靶点如黑质网状部和球状体 苍白球 最后，我们将继续评估解剖和 安非他明和可卡因的病理后果 使用酪氨酸羟化酶对大鼠脑给药 免疫细胞化学，Fink-Heimer法鉴定 尾状核和大脑皮层变性，以及 生物化学分析潜在的单胺消耗， 这些网站。

This application seeks renewal of research support for five years to study the sites and mechanisms of action of psychomotor stimulant drugs, including amphetamine and cocaine. Experiments are proposed to determine the mechanisms underlying alterations in catecholaminergic and non-catecholaminergic neuronal terminal excitability, including an analysis of the influence of cocaine on catecholaminergic terminal excitability and whether changes in terminal excitability of dopaminergic neurons in the rat brain occur in the chronically implanted, behaving animal. An attempt will be made to collect converging evidence regarding the identity and postsynaptic target of dopaminergic synapses made in neostriatum and to assess the relation of dopaminergic synapses made in neostriatum to its compartmentalization into the dopaminergic islandic or striosomal and matrix compartments. Further experiments are proposed to assess the consequences of amphetamine administration on neuronal activity in neostriatal targets such as pars reticulata of substantia nigra and globus pallidus. Finally, we will continue to assess the anatomical and pathological consequences of amphetamine and cocaine administration on the rat brain using tyrosine hydroxylase immunocytochemistry, the Fink-Heimer method for identifying degeneration in caudate nucleus and cerebral cortex, and biochemical analysis of potential monoamine depletions from these sites.