MECHANISMS OF ACTION OF DRUGS OF ABUSE--AMPHETAMINE

滥用药物--安非他明的作用机制

• 批准号: 2390981
• 负责人: PHILIP M GROVES
• 金额: $ 57.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2390981
• 关键词: amphetamines; antidepressants; behavioral medicine; brain metabolism; central nervous system stimulants; cocaine; corpus striatum; dopamine; dopamine receptor; dosage; drug abuse; drug metabolism; electron microscopy; electrophysiology; histochemistry /cytochemistry; immunocytochemistry; laboratory rat; locus coeruleus; neurochemistry; neurotransmitter receptor; pharmacokinetics; stereotaxic techniques; substantia nigra; synapses

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.

该申请寻求更新五年的研究支持 研究精神运动的作用部位和机制 兴奋剂药物，包括安非他明和可卡因。 实验 建议确定潜在改变的机制 在儿茶酚胺能和非儿茶酚胺能神经元末梢 兴奋性，包括分析可卡因对 儿茶酚胺能终末兴奋性以及是否发生变化 大鼠大脑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中。 一次尝试 将收集有关身份的一致证据 和多巴胺能突触的突触后目标 新纹状体并评估多巴胺能突触的关系 在新纹状体中制造，将其划分为 多巴胺能岛状或纹状体和基质区室。 建议进一步进行实验来评估后果 安非他明给药对新纹状体神经元活动的影响 黑质网状部和球状部等目标 苍白球。 最后，我们将继续评估解剖学和 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进行给药 免疫细胞化学，Fink-Heimer 鉴定方法 尾状核和大脑皮层变性，以及 潜在单胺消耗的生化分析 这些网站。

项目成果

Do antidromic latency jumps indicate axonal branching in nigrostriatal and hypothalamo-neurohypophysial neurons?

逆向潜伏期跳跃是否表明黑质纹状体和下丘脑-神经垂体神经元的轴突分支？

• DOI: 10.1016/0006-8993(87)90760-8
• 发表时间: 1987
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Klemfuss,H;Young,SJ;Groves,PM
• 通讯作者: Groves,PM

Cocaine, in contrast to D-amphetamine, does not cause axonal terminal degeneration in neostriatum and agranular frontal cortex of Long-Evans rats.

与 D-苯丙胺相比，可卡因不会引起 Long-Evans 大鼠新纹状体和无颗粒额叶皮层的轴突变性。

• DOI: 10.1016/0024-3205(88)90307-4
• 发表时间: 1988
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Ryan,LJ;Martone,ME;Linder,JC;Groves,PM
• 通讯作者: Groves,PM

Neurophysiological consequences of amphetamine administration.

安非他明给药的神经生理学后果。

• 发表时间: 1988
• 期刊: NIDA research monograph
• 作者: Groves,P;Ryan,L;Diana,M;Gariano,R
• 通讯作者: Gariano,R

Modulation of dopaminergic terminal excitability by D1 selective agents.

D1 选择剂调节多巴胺能末端兴奋性。

• DOI: 10.1016/0028-3908(89)90074-9
• 发表时间: 1989
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Diana,M;Young,SJ;Groves,PM
• 通讯作者: Groves,PM

Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of potassium channel blockers.

自身受体介导的多巴胺能末端兴奋性变化：钾通道阻滞剂的作用。

• DOI: 10.1016/0006-8993(86)91596-9
• 发表时间: 1986
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Tepper,JM;Sawyer,SF;Young,SJ;Groves,PM
• 通讯作者: Groves,PM