MECHANISMS OF ACTION OF DRUGS OF ABUSE--AMPHETAMINE

此申请寻求续订五年的研究支持 研究精神运动的作用部位和机制 兴奋剂，包括苯丙胺和可卡因。实验 被提议用来确定改变背后的机制 在儿茶酚胺能和非儿茶酚胺能神经元终末 兴奋性，包括分析可卡因对 儿茶酚胺能终末兴奋性及其是否改变 大鼠脑内多巴胺能神经元的终末兴奋性 发生在长期植入、行为正常的动物体内。一次尝试 将被要求收集关于身份的聚合证据 和多巴胺能突触的突触后靶点 新纹状体和多巴胺能突触之间的关系 在新纹状体中制造到它被分割成 多巴胺能岛状或纹状体和基质隔室。 建议进行进一步的实验，以评估 苯丙胺对新生纹状体神经元活动的影响 黑质网状部和球部等靶点 苍白球。最后，我们将继续评估解剖和 苯丙胺和可卡因的病理后果 酪氨酸羟基酶对大鼠脑内的作用 免疫细胞化学，芬克-海默法鉴定 尾状核和大脑皮层变性，以及 烟尘中潜在单胺消耗的生化分析 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.