Methamphetamine Effects on Dendrodendritic Dopamine Transmission in the VTA

甲基苯丙胺对 VTA 树突状多巴胺传递的影响

• 批准号: 7615534
• 负责人: Michael J Beckstead
• 金额: $ 14.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615534
• 关键词: Affect; Animals; Autoreceptors; Behavior; Behavioral; Calcium; Country; Dendrodendritic Synapse; Development Plans; Dopamine; Drug abuse; Drug usage; Electrophysiology (science); Experimental Designs; Goals; Human; Injection of therapeutic agent; Intervention; Lead; Learning; Link; Mediating; Mentored Research Scientist Development Award; Mentorship; Methamphetamine; Modeling; Mus; Neurosciences; Patients; Pattern; Pharmaceutical Preparations; Play; Procedures; Psychological reinforcement; Research Personnel; Resources; Role; Self Administration; Self-Administered; Site; Synapses; Synaptic Potentials; Synaptic plasticity; Techniques; Testing; Training; Ventral Tegmental Area; addiction; base; brain surgery; career; career development; dopaminergic neuron; investigator training; neuroadaptation; neurophysiology; novel; prevent; psychostimulant; research study; tool; transmission process

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award (K01) proposes to investigate the neurophysiological consequences of methamphetamine self-administration while providing the candidate (Dr. Michael Beckstead) with training in behavioral neuroscience. Dr. Beckstead's immediate goals include learning behavioral techniques including stereotaxic surgeries, brain site-specific injections, methamphetamine self administration procedures, and experimental design and interpretation of models of psychostimulant administration. In addition to the scientific aims of the studies presented, the ultimate goal of the proposal is to train the investigator with behavioral techniques that, along with established expertise in electrophysiology, will form the basis for a career as an independent investigator. The career development plan involves mentorship in behavioral techniques from an established behavioral neuroscientist (Dr. Gregory Mark) while utilizing the resources and expertise of one of the top behavioral departments in the country. The experimental procedures will investigate the hypothesized relationship between methamphetamine self-administration, intracellular calcium levels, and dendrodendritic dopamine transmission in the ventral tegmental area of mice. Methamphetamine induces synaptic plasticity and D2 dopamine autoreceptor subsensitivity, but the mechanisms involved are poorly understood. Furthermore, no study has investigated the role of synaptic plasticity on methamphetamine self-administration. Using recently discovered tools including a synaptic potential mediated by dopamine and a novel form of plasticity at dopamine synapses, the experiments will determine if dopamine plasticity plays a role in methamphetamine self-administration. Relevance: Determining the neurophysiological consequences of methamphetamine self-administration is the first step in identifying intervention strategies to prevent and treat human drug abuse. A better understanding of the neural adaptations associated with drug use and administration may help to explain why some methamphetamine users become addicted to the drug, and may lead to treatments to help patients break the difficult cycle of addiction.

描述(由申请人提供)：这项指导研究科学家发展奖(K01)建议调查甲基苯丙胺自我给药的神经生理学后果，同时为候选人(Michael Beckstead博士)提供行为神经科学方面的培训。贝克斯特德博士的近期目标包括学习行为技术，包括立体定向手术、脑部特定部位注射、甲基苯丙胺自我给药程序，以及精神刺激剂给药模型的实验设计和解释。除了提出的研究的科学目标外，该提案的最终目标是培训调查员掌握行为技术，这些技术加上电生理学方面的成熟专业知识，将构成作为独立调查员的职业生涯的基础。职业发展计划包括由知名行为神经学家(格雷戈里·马克博士)指导行为技术，同时利用美国顶尖行为部门的资源和专业知识。实验程序将调查甲基苯丙胺自身给药、细胞内钙水平和小鼠腹侧被盖区树突状细胞多巴胺传递之间的假设关系。甲基苯丙胺诱导突触可塑性和D2多巴胺自身受体亚敏感性，但涉及的机制尚不清楚。此外，还没有研究探讨突触可塑性在甲基苯丙胺自我给药中的作用。利用最近发现的工具，包括多巴胺介导的突触电位和多巴胺突触的一种新形式的可塑性，这些实验将确定多巴胺的可塑性是否在甲基苯丙胺自我给药中发挥作用。相关性：确定甲基苯丙胺自我给药的神经生理学后果是确定预防和治疗人类药物滥用的干预策略的第一步。更好地了解与药物使用和给药相关的神经适应可能有助于解释为什么一些甲基苯丙胺使用者会对药物上瘾，并可能导致治疗方法，帮助患者打破成瘾的困难循环。