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本科生将参加正在进行的研究 在科学家委员会的指导下计划。这些关于啮齿动物的研究 将使用电生理，神经药物和解剖学 方法以揭示尾状刺激药物的作用 核。该细胞核及其多巴胺能的输入 是刺激性药物作用的重要部位，包括 苯丙胺和可卡因。此外，这个主要综合区域 基底神经节是亨廷顿和 帕金森氏病。以及阐明滥用药物的作用， 这项研究将揭示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，突触前的相互作用发生在 多巴胺能乳清层和谷氨酸能的尾巴 皮质纹状体传入。这些相互作用似乎是由 位于传入端子中的自动和异发子的激活 神经递质的区域是从附近突触释放的。这些 突触前的相互作用可能是行动的重要基因座 刺激性药物。学生将有机会参加 使用末端轴突测量的电生理研究 电兴奋性研究这些相互作用。细胞外 记录和终端兴奋性技术也将用于 检查两个发射特性的可能改变 黑质的多巴胺能神经元和自身受体的变化 这些神经元终端的反馈调节 与大鼠对行为敏化有关的细胞核 苯丙胺。 我们以前已经观察到产前可卡因会产生 大鼠尾状核的显着改变。学生会 参与使用相关光和电子的结构研究 基底神经节和相关区域的显微镜检查。 这些 实验将使用免疫细胞化学技术，图像分析和 计算机协助三维重建，以进一步阐明 这些可卡因暴露的动物的大脑引起的变化。 还提出了解剖学研究以准确表征 多巴胺能突触的密度，突触后部位和 这些突触后站点与其他传入的关系之间的关系 尾状神经元。