BASAL GANGLIA ANATOMY AND PHYSIOLOGY--MECHANISMS OF ACTION OF DRUGS OF ABUSE

基底神经节解剖学和生理学——滥用药物的作用机制

• 批准号: 6271780
• 负责人: PHILIP M GROVES
• 金额: $ 5.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6271780
• 关键词: afferent nerve; amphetamines; basal ganglia; caudate nucleus; cocaine; computer simulation; dopamine; drug abuse; drug interactions; drug receptors; electron microscopy; electrophysiology; image processing; immunocytochemistry; laboratory rat; neural information processing; neuroanatomy; neuropharmacology; neurophysiology; neurotransmitters; nicotine; synapses

MBRS undergraduate students will participate in an on-going research program under the guidance of scientist-mentors. These studies on rodents will use electrophysiological, neuropharmacological, and anatomical approaches to reveal the actions of stimulant drugs in the caudate nucleus. This nucleus and its dopaminergic input from the substantia nigra are prominent sites for the action of stimulant drugs, including amphetamine and cocaine. In addition, this major integrative area of the basal ganglia is a significant locus for the pathology of Huntington's and Parkinson's disease. As well as elucidating the action of drugs of abuse, this research will reveal fundamental aspects of neuronal processing in the caudate nucleus and its associated afferent systems. Recent evidence suggests that presynaptic interactions occur in the caudate between dopaminergic nigrostriatal and glutamatergic corticostriatal afferents. These interactions appear to result from the activation of auto- and heteroreceptors located in afferent terminal regions by neurotransmitter released from nearby synapses. These presynaptic interactions may be an important locus for the action of stimulant drugs. Students will have the opportunity to participate in electrophysiological studies employing the measurement of terminal axon electrical excitability to investigate these interactions. Extracellular recording and the terminal excitability technique will also be used to examine possible alterations in both the firing properties of the dopaminergic neurons of the substantia nigra and changes in autoreceptor feedback regulation of the terminals of these neurons within the caudate nucleus related to the behavioral sensitization of the rats to amphetamine. We have previously observed that prenatal cocaine administration produces significant alterations in the rat caudate nucleus. Students will participate in structural studies employing correlated light and electron microscopic examination of basal ganglia and related regions. These experiments will use immunocytochemical techniques, image analysis, and computer assisted three-dimensional reconstruction to further elucidate the changes induced in the brains of these cocaine exposed animals. Anatomical studies are also proposed to accurately characterize the density of dopaminergic synapses, their postsynaptic sites, and the relation between these post-synaptic sites and those of other afferents to caudate neurons.

MBRS本科生将参与一项正在进行的研究 项目在科学家导师的指导下进行。这些关于啮齿动物的研究 将使用电生理学、神经药理学和解剖学 揭示刺激性药物在尾状核作用的途径 原子核。这个核团及其来自黑质的多巴胺能传入 是兴奋剂作用的显著场所，包括 安非他命和可卡因。此外，中国的这一主要综合领域 基底节是亨廷顿病的重要病理部位。 帕金森氏症。除了阐明滥用药物的作用外， 这项研究将揭示脑内神经元处理的基本方面 尾状核及其相关的传入系统。 最近的证据表明，突触前相互作用发生在 多巴胺能黑质纹状体和谷氨酸能神经元之间的尾状核 皮质纹状体传入神经。这些相互作用似乎是由于 传入终末自体受体和异体受体的激活 由附近突触释放的神经递质所决定的区域。这些 突触前相互作用可能是突触运动的重要部位 兴奋剂。学生们将有机会参加 终末轴突测量的电生理学研究 电兴奋性来研究这些相互作用。胞外 录音和终端兴奋性技术也将用于 检查在两个激发属性中可能的更改 黑质多巴胺能神经元及其自身受体的变化 尾状核内这些神经元终末的反馈调节 与大鼠行为敏感化有关的核团 安非他命。 我们之前已经观察到，产前服用可卡因会产生 大鼠尾状核的明显改变。学生们将 参与使用相关光和电子的结构研究 对基底节及相关区域进行显微镜检查。这些 实验将使用免疫细胞化学技术、图像分析和 计算机辅助三维重建以进一步阐明 这些暴露在可卡因中的动物的大脑中诱导的变化。 还建议进行解剖学研究，以准确地描述 多巴胺能突触的密度、它们的突触后部位以及 这些突触后部位与其他传入神经元的关系 尾状神经元。