NOVEL MODES OF ACTIONS OF ABUSED DRUGS

滥用药物的新作用模式

• 批准号: 3075384
• 负责人: PHILIP M GROVES
• 金额: $ 5.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-06-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3075384
• 关键词: adrenergic receptor; afferent nerve; amphetamines; behavioral medicine; central neural pathway /tract; cocaine; corpus striatum; dopamine receptor; drug abuse; drug metabolism; electrophysiology; histochemistry /cytochemistry; immunochemistry; immunocytochemistry; laboratory rat; lenticular nucleus; motor cortex; neural degeneration; neuronal transport; nontherapeutic iontophoresis; psychotropic drugs; receptor sensitivity; substantia nigra; synapses

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.

建议进行实验以确定潜在的机制。 儿茶酚胺能和非儿茶酚胺能神经元的变化 终端兴奋性，包括对 可卡因对儿茶酚胺能终末兴奋性的影响 大鼠多巴胺能神经元终末兴奋性的变化 大脑发生在长期植入的、行为正常的动物身上。一个 将尝试收集关于以下方面的汇聚证据 多巴胺能突触的识别和突触后靶点 并评估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 安非他明和可卡因给药的病理后果 用酪氨酸羟基酶免疫细胞化学方法对大鼠脑进行染色， 识别尾状核变性的Fink-Heier方法 核和大脑皮层，以及电势的生化分析 这些部位的单胺消耗。