Guidance molecules interact to orchestrate dopamine plasticity in adulthood

引导分子相互作用以协调成年期的多巴胺可塑性

• 批准号: RGPIN-2015-04819
• 负责人: Flores, Cecilia
• 金额: $ 2.91万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=687752
• 关键词: Guidance; molecules; interact; orchestrate; dopamine

The dopamine systems of the brain are involved in cognition, motor activity, motivation and reward. These systems and their connections are remarkably plastic, undergoing changes throughout life. Repeated exposure to stimulant drugs, such as amphetamine, results in changes in dopamine systems resulting in long-lasting increases in sensitivity to the effects that these drugs, and to other life events that activate the dopamine systems. The general aim of my research project is to identify mechanisms that bring about changes in sensitivity in dopamine function and behavior in adulthood, rendering individuals more (or less) vulnerable to subsequent exposure to drugs or to stressors. To this end I will study how amphetamine induces such changes in the adult brain. Identification of these processes will have important implications for our understanding of how `experience' can alter dopamine circuitry and, in turn, dopamine-mediated behaviors. The enduring nature of changes in the dopamine system in the adult brain suggests reorganization of the circuitry by re-activation of factors that are normally involved in organizing neuronal wiring during development. Netrin-1 is a protein that plays a fundamental role in the organization of neuronal connectivity during development and we have recently shown that (1) netrin-1 receptors are highly expressed by dopamine neurons in the adult brain, (2) repeated amphetamine exposure in the adult upregulates the expression of netrin-1 receptors, (3) netrin-1 receptor upregulation by amphetamine is required for the development of amphetamine induced dopamine plasticity. This research proposal is now aimed at identifying how precisely netrin-1 and netrin-1 receptors mediate amphetamine-induced dopamine plasticity in the adult.**

大脑的多巴胺系统参与认知，运动活动，动机和奖励。这些系统及其连接非常塑料，整个生命都会发生变化。反复接触刺激药物（例如苯丙胺）导致多巴胺系统的变化，导致对这些药物的影响的敏感性增加，以及激活多巴胺系统的其他生命事件。我的研究项目的总体目的是确定使多巴胺功能和成年行为敏感性变化的机制，从而使个人更容易受到随后接触药物或压力源的影响。为此，我将研究苯丙胺如何引起成人大脑的这种变化。这些过程的识别将对我们对“体验”如何改变多巴胺电路以及多巴胺介导的行为的理解具有重要意义。成人大脑中多巴胺系统变化的持久性质表明，通过重新激活通常涉及开发过程中神经元接线的因素来重组电路。 Netrin-1是一种蛋白质，在发育过程中在神经元连通性的组织中起着基本作用，我们最近表明（1）Netrin-1受体在成人大脑中多巴胺神经元高度表达，（2）成人在成年人中反复暴露于成年人的netrin-1受体的表达，（3）NetRemin in NetRemine in NetRemine in NetRegine in NetRegine in NetRegine aftremine in NetRegine aftremine in Netregine aftemine（3）诱导多巴胺可塑性。该研究建议现在旨在确定Netrin-1和Netrin-1受体如何介导成年人中苯丙胺诱导的多巴胺可塑性。**