NEURAL AND MOLECULAR MECHANISMS IN STRIATAL LEARNING

纹状体学习中的神经和分子机制

• 批准号: 2872105
• 负责人: CARMEN Sara MALDONADO-VLAAR
• 金额: $ 10.12万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-20 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2872105
• 关键词: antisense nucleic acid; association learning; behavior test; behavioral /social science research tag; cocaine; corpus striatum; drug abuse; drug addiction; excitatory aminoacid; glutamate receptor; laboratory rat; learning; memory; microinjections; motivation; nucleus accumbens; protein kinase C; reinforcer; self medication; substance abuse related behavior

DESCRIPTION: (Applicant's Abstract) Drug abuse has become a major social and medical problem in the United States, South America and Europe. Presently, it is estimated that there are over 2 million regular drug users in the USA. One of the main goals of neurobiological research is to study the different neural systems and molecular mechanisms involved in drug addiction. The nucleus accumbens and other areas of the corpus striatum have previously been implicated in mediating the motor activation and reinforcing effects of psychostimulant drugs such as cocaine. In addition, studies have demonstrated that these subregions of the striatum also regulate different learning and memory functions and that excitatory amino acid (EAA) neurotransmission from cortical and limbic projections to these striatal regions modulate these functions. The metabotropic glutamate receptor (mGluRs) is a type of EAA receptor found in the striatum that seems to have modulatory effects in synaptic plasticity and learning. The current proposal seeks to further investigate EAA neurotransmission and the role of protein kinase C within the different subregions of the corpus striatum, using a behavioral-pharmacological-molecular approach in the rat. To accomplish this goal, direct brain microinfusions of experimental drugs will be utilized in conjunction with behavioral paradigms that measure: spatial learning, intravenous cocaine self-administration responding and the reinstatement of cocaine seeking behavior. There are two major goals of the proposed experiments: 1) To characterize the role that mGluRs within the corpus striatum play in controlling learning related to both normal and cocaine-induced behavioral response. 2) To examine the role of Protein Kinase C activation within different striatal regions in distinct striatal learning functions. Results from the proposed research plan may provide new knowledge on: 1) the functional roles of EAA-receptors and, specifically the mGluRs, in the corpus striatum, 2) the molecular mechanisms controlled by PKC that are involved in the modulation of different forms of striatal learning, and 3) the role of EAA receptors and PKC activity within the nucleus accumbens in mediating cocaine reinforcement and eliciting cocaine seeking behavior.

描述：（申请人摘要）吸毒已成为一个主要的社会问题 以及美国、南美和欧洲的医疗问题。 目前，估计有超过200万经常吸毒者 在美国。 神经生物学研究的主要目标之一是研究 药物涉及的不同神经系统和分子机制 瘾。 伏隔核和纹状体的其他区域 以前曾涉及介导运动激活和 加强可卡因等精神兴奋药物的作用。 此外， 研究表明，纹状体的这些分区也 调节不同的学习和记忆功能，兴奋性氨基酸 从皮质和边缘投射到这些的酸性（EAA）神经传递 纹状体区域调节这些功能。 代谢型谷氨酸 受体 (mGluRs) 是纹状体中发现的一种 EAA 受体，似乎 对突触可塑性和学习具有调节作用。 目前的 该提案旨在进一步研究 EAA 神经传递及其作用 纹状体不同亚区域内的蛋白激酶 C， 在大鼠身上使用行为药理学分子方法。 到 为了实现这一目标，实验药物的直接脑部微量输注将 与测量以下行为范式结合使用： 学习、静脉注射可卡因自我给药反应和 恢复可卡因寻求行为。 该组织有两个主要目标 建议的实验：1）表征 mGluRs 在 纹状体在控制与正常和 可卡因引起的行为反应。 2) 检查蛋白质的作用 不同纹状体不同纹状体区域内的激酶 C 激活 学习功能。 拟议研究计划的结果可能会提供新的 有关以下方面的知识：1) EAA 受体的功能作用，特别是 mGluRs，在纹状体中，2）控制的分子机制 PKC 参与不同形式纹状体的调节 学习，以及 3) EAA 受体和 PKC 活性在 伏隔核介导可卡因强化和引发可卡因 寻求行为。