NEURAL AND MOLECULAR MECHANISMS IN STRIATAL LEARNING

纹状体学习中的神经和分子机制

• 批准号: 2563142
• 负责人: CARMEN Sara MALDONADO-VLAAR
• 金额: $ 13.04万
• 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/2563142
• 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

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：（申请人的摘要）药物滥用已成为主要社会 以及美国，南美和欧洲的医疗问题。 目前，据估计有超过200万普通吸毒者 在美国。 神经生物学研究的主要目标之一是研究 参与药物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 以前曾与介导运动激活有关 加强心理刺激药物（例如可卡因）的作用。 此外， 研究表明，纹状体的这些子区域也 调节不同的学习和记忆功能和兴奋性氨基 酸（EAA）从皮质和边缘投影到这些的神经传递 纹状体区域调节这些功能。 代谢性谷氨酸 受体（mglurs）是在纹状体中发现的一种EAA受体 在突触可塑性和学习中具有调节作用。 电流 提案旨在进一步调查EAA神经传递和 蛋白激酶C在纹状体的不同子区域内， 使用大鼠的行为 - 药理学方法。 到 实现这一目标，实验药物的直接大脑微型诱发将 与行为范式一起使用：空间 学习，可卡因自我管理的反应和 恢复可卡因寻求行为。 有两个主要目标 提出的实验：1）表征mglurs在 纹状体在控制与正常和正常有关的学习方面发挥了作用 可卡因诱导的行为反应。 2）检查蛋白质的作用 不同纹状体区域内不同纹状体的激酶C激活 学习功能。 拟议的研究计划的结果可能会提供新的 知识：1）EAA受体的功能作用，特别是 纹状体中的mglurs，2）控制的分子机制 由PKC涉及不同形式的纹状体的调节 学习，3）EAA受体和PKC活性在 伏隔核介导可卡因加固和引起可卡因 寻求行为。