MECHANISM OF ACTION OF DRUGS OF ABUSE--AMPHETAMINE

滥用药物--安非他明的作用机制

基本信息

  • 批准号:
    6515356
  • 负责人:
  • 金额:
    $ 17.78万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1993
  • 资助国家:
    美国
  • 起止时间:
    1993-06-01 至 2005-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: (Adapted From The Applicant's Abstract) This application seeks renewal of research support to continue to study the sites and mechanisms of action of psychomotor stimulants. Its general aim is to study the effects of amphetamine on striatal glutamate and dopamine neurotransmission and the sites of termination of glutamate and dopamine axons relative to the different neostriatal output cells. Specifically, it will address three issues related to the effects of systemic amphetamine: the presynaptic mechanisms contributing to neostriatal changes associated with addiction, and the circuitry that brings about the amphetamine-induced increase in neuronal activity of the direct striatal output pathway. The motor effects of these drugs depend on their ability to increase dopamine (DA) transmission. Several motor responses are enhanced by repeated amphetamine administration; a phenomenon termed behavioral sensitization. Changes in the sensitivity of DA somatodendritic and terminal axon autoreceptors may contribute to behavioral sensitization. Experiments are proposed using terminal excitability, an in vivo electro- physiological measure of presynaptic receptor stimulation, and microdialysis to further study the bases for presynaptic changes in nigrostriatal DA axon terminals in sensitized rats. DA terminal fields in nucleus accumbens and prefrontal cortex will also be examined. Alterations in glutamatergic transmission may also be critical in the development of sensitization. Excitability measurements will assess possible presynaptic changes in the glutamatergic afferents to the neostriatum, nucleus accumbens and ventral tegmental area. Other studies will examine the relation between impulse-induced long-lasting changes in presynaptic corticostriatal excitability and postsynaptic expressions of long- term potentiation or depression. Electron microscopic studies are proposed to further elucidate the neostriatal circuitry involving the DA and glutamate afferent systems. It will be determined whether DA inputs onto spiny dendrites are associated with inputs from specific cortical and thalamic regions and if these patterns of convergence differ for spiny neurons identified as belonging to the direct and indirect output pathways. The thalamus is a major excitatory input to the striatum, yet little is known regarding differences in innervation from specific thalamic regions. Differences in the thalamic input onto cholinergic and spiny neurons participating in the two output pathways will be examined and the morphology and other afferents of these cells determined. The possibility of nonsynaptic release sites on nigrostriatal DA afferents will be assessed by labeling components of the release mechanism and then correlating them with the locations of dopamine receptors.
产品说明:(改编自申请人摘要)本申请寻求研究支持的更新,以继续研究精神兴奋剂的作用部位和机制。其总体目标是研究安非他明对纹状体谷氨酸和多巴胺神经传递的影响,以及谷氨酸和多巴胺轴突相对于不同的新纹状体输出细胞的终止位点。具体而言,它将解决三个问题,系统性安非他明的影响:突触前机制有助于与成瘾相关的新纹状体的变化,和电路,带来安非他明诱导的直接纹状体输出通路的神经元活动的增加。这些药物的运动效应取决于它们增加多巴胺(DA)传递的能力。几种运动反应被反复服用安非他明所增强,这种现象被称为行为敏化。DA体树突和终末轴突自身受体敏感性的变化可能有助于行为敏化。本实验拟用末梢兴奋性(一种突触前受体刺激的在体电生理测量)和微透析技术进一步研究致敏大鼠黑质纹状体DA轴突末梢突触前变化的基础。还将检查中脑核和前额叶皮层中的DA终末野。代谢能传递的改变也可能在致敏的发展中起关键作用。兴奋性测量将评估可能的突触前变化的神经元传入到新纹状体,核腹侧被盖区。其他的研究将检查冲动引起的突触前皮质纹状体兴奋性的长期变化与突触后长时程增强或抑制的表达之间的关系。电子显微镜研究提出进一步阐明新纹状体电路涉及DA和谷氨酸传入系统。它将被确定是否DA输入到多刺树突与特定的皮质和丘脑区域的输入,如果这些模式的收敛不同的多刺神经元被确定为属于直接和间接的输出途径。丘脑是纹状体的主要兴奋性输入,但对特定丘脑区域的神经支配差异知之甚少。将检查丘脑输入到参与两个输出通路的胆碱能和多刺神经元的差异,并确定这些细胞的形态和其他传入。黑质纹状体DA传入神经上的非突触释放位点的可能性将通过标记释放机制的组分,然后将它们与多巴胺受体的位置相关联来评估。

项目成果

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RONALD KUCZENSKI其他文献

RONALD KUCZENSKI的其他文献

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{{ truncateString('RONALD KUCZENSKI', 18)}}的其他基金

NEUROCHEMISTRY OF MODAFINIL-MA INTERACTION IN RAT BRAIN
大鼠脑中莫达非尼-MA 相互作用的神经化学
  • 批准号:
    7689052
  • 财政年份:
    2008
  • 资助金额:
    $ 17.78万
  • 项目类别:
Simulated Human Pharmacokinetics in Rat: Methylphenidate
大鼠模拟人体药代动力学:哌甲酯
  • 批准号:
    7239047
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
NEUROCHEMISTRY OF MODAFINIL-MA INTERACTION IN RAT BRAIN
大鼠脑中莫达非尼-MA 相互作用的神经化学
  • 批准号:
    7556055
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
Simulated Human Pharmacokinetics in Rat: Methylphenidate
大鼠模拟人体药代动力学:哌甲酯
  • 批准号:
    7365252
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
NEUROCHEMISTRY OF MODAFINIL-MA INTERACTION IN RAT BRAIN
大鼠脑中莫达非尼-MA 相互作用的神经化学
  • 批准号:
    7222339
  • 财政年份:
    2006
  • 资助金额:
    $ 17.78万
  • 项目类别:
MECHANISM OF ACTION OF DRUGS OF ABUSE--AMPHETAMINE
滥用药物--安非他明的作用机制
  • 批准号:
    6634155
  • 财政年份:
    1993
  • 资助金额:
    $ 17.78万
  • 项目类别:
BRAIN NORADRENERGIC NEURONS, PEPTIDES, AND STRESS
大脑去甲肾上腺素能神经元、肽和压力
  • 批准号:
    2244848
  • 财政年份:
    1985
  • 资助金额:
    $ 17.78万
  • 项目类别:
CHRONIC DRUGS: CNS BIOCHEMISTRY & BEHAVIOR
慢性药物:中枢神经系统生物化学
  • 批准号:
    3209392
  • 财政年份:
    1985
  • 资助金额:
    $ 17.78万
  • 项目类别:
CHRONIC DRUGS: CNS BIOCHEMISTRY & BEHAVIOR
慢性药物:中枢神经系统生物化学
  • 批准号:
    3209387
  • 财政年份:
    1985
  • 资助金额:
    $ 17.78万
  • 项目类别:
CHRONIC DRUGS: CNS BIOCHEMISTRY AND BEHAVIOR
慢性药物:中枢神经系统生物化学和行为
  • 批准号:
    3209393
  • 财政年份:
    1985
  • 资助金额:
    $ 17.78万
  • 项目类别:
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