Methamphetamine, procedural learning, and plasticity

甲基苯丙胺、程序性学习和可塑性

• 批准号: 6938032
• 负责人: DAVID Paxton DABERKOW
• 金额: $ 2.89万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938032
• 关键词: amines; autoradiography; basal ganglia; behavior test; behavioral /social science research tag; drug abuse; drug addiction; fluorescent in situ hybridization; fos protein; gene expression; gene induction /repression; image processing; in situ hybridization; laboratory rat; learning; memory; methamphetamine; neural plasticity; neurochemistry; neurophysiology; neurotoxicology; nucleic acid probes; predoctoral investigator; regulatory gene; statistics /biometry; synapses

DESCRIPTION (provided by applicant): The major goal of this project will be to examine how methamphetamine (METH)-induced monoamine depletions affect basal ganglia-mediated learning and the expression of three molecules thought to be critically involved in learning and memory function (c-fos, zif268, arc) in the dorsal striatum. We hypothesize that METH-induced monoamine depletions will impair basal ganglia-mediated learning and alter the normal expression of molecules associated with synaptic plasticity in the dorsal striatum. The basic experimental design will be to treat rats with a neurotoxic regimen of METH, known to induce monoamine depletions in the basal ganglia. These METH-treated rats, along with controls, will then be trained on a basal gangliadependent motor-response learning task in a plus maze. Once the rats meet motor-response learning criterion, the brains will be removed and processed for in situ hybridization to identify c-fos, zif268, and arc mRNA expression in identified efferent neuron populations of the dorsal striatum. This work will lead to a better understanding of how METH abuse affects normal learning and memory function and will provide insight into how changes in brain chemistry induced by drugs of abuse might lead to drug addiction.

描述（由申请人提供）： 该项目的主要目标是研究甲基苯丙胺 (METH) 诱导的单胺消耗如何影响基底神经节介导的学习以及被认为与学习和记忆功能至关重要的三种分子（c-fos、zif268、arc）的表达在背侧纹状体。我们假设 METH 诱导的单胺消耗会损害基底神经节介导的学习，并改变背侧纹状体中与突触可塑性相关的分子的正常表达。基本的实验设计是用神经毒性的冰毒疗法治疗大鼠，冰毒会导致基底神经节单胺消耗。然后，这些接受冰毒治疗的大鼠以及对照组的大鼠将在正号迷宫中接受基底神经节依赖性运动反应学习任务的训练。一旦大鼠满足运动反应学习标准，将取出大脑并进行原位杂交处理，以识别背侧纹状体传出神经元群体中的 c-fos、zif268 和 arc mRNA 表达。这项工作将有助于更好地了解冰毒滥用如何影响正常的学习和记忆功能，并将深入了解滥用药物引起的大脑化学变化如何可能导致药物成瘾。