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: 7254296
• 负责人: Michael J Beckstead
• 金额: $ 11.33万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 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/7254296
• 关键词: Affect; Animals; Autoreceptors; Behavior; Behavioral; Calcium; Chromosome Pairing; 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; 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）：这项指导的研究科学家发展奖（K01）提议研究甲基苯丙胺自我管理的神经生理学后果，同时为候选人（Michael Beckstead博士）进行行为神经科学的培训。贝克斯特德博士的近期目标包括学习行为技术，包括立体定位手术，大脑特定注射，甲基苯丙胺自我给药程序以及对心理刺激剂的模型的实验设计和解释。除了提出的研究的科学目的外，该提案的最终目标是培训研究人员的行为技术，这些技术以及既定的电生理学专业知识将成为作为独立研究者职业的基础。职业发展计划涉及来自既定行为神经科学家（Gregory Mark博士）的行为技术的指导，同时利用该国最高行为部门之一的资源和专业知识。实验程序将调查甲基苯丙胺自我给药，细胞内钙水平和小鼠腹侧偏段区域的树突状多巴胺传播之间的假设关系。甲基苯丙胺诱导突触可塑性和D2多巴胺自身受体降低性，但所涉及的机制知之甚少。此外，尚无研究研究突触可塑性对甲基苯丙胺自我给药的作用。使用最近发现的工具，包括由多巴胺介导的突触势和多巴胺突触中新型的可塑性形式，实验将确定多巴胺可塑性是否在甲基苯丙胺的自我加入中起作用。相关性：确定甲基苯丙胺自我给药的神经生理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性可能有助于解释为什么一些甲基苯丙胺使用者会沉迷于药物，并可能导致治疗以帮助患者打破困难的成瘾循环。