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.

（申请人摘要）药物滥用已成为社会一大问题