权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Endocannabinoid regulation of dopamine function and reinforcement

内源性大麻素对多巴胺功能的调节和强化

基本信息

批准号：
9256881
负责人：
Daniel Patrick Covey
金额：
$ 5.92万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-13 至 2020-02-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9256881
关键词：
2-arachidonylglycerol Address Adverse effects Agonist Animals Appetitive Behavior Attenuated Automobile Driving Behavior CNR1 gene Cannabinoids Clinical Cues Data Desire for food Development Disease Dopamine Drug abuse Drug effect disorder Drug usage Elements Endocannabinoids Enzymes Future Genetic Recombination In Vitro Incentives Individual Infusion procedures Laboratories Ligands Measures Mediating MicroRNAs Modeling Monitor Motivation Mus Mutagenesis Neurons Nucleus Accumbens Obesity Optics Periodicity Pharmaceutical Preparations Pharmacology Pharmacotherapy Population Positive Reinforcements Predictive Value Presynaptic Terminals Psychological reinforcement Psychopathology Receptor Signaling Regulation Response Latencies Rewards Scanning Self Stimulation Side Specificity Techniques Testing Time Tissues United States Ventral Tegmental Area Work base cell type craving dopamine system dopaminergic neuron economic cost endocannabinoid signaling endogenous cannabinoid system health economics heuristics knock-down lipoprotein lipase neural circuit neurophysiology novel optogenetics pre-clinical presynaptic relating to nervous system therapy development

项目摘要

Project Summary/Abstract Maladaptive forms of reward seeking that support drug abuse and obesity exact an enormous toll on individual and economic health. A mounting body of preclinical and clinical work demonstrates that the endocannabinoid system powerfully regulates the motivational impact of rewards. While pharmacotherapies targeting endocannabinoid function to treat disordered reward seeking are efficacious, this approach has been hindered due to non-specific drug actions and unacceptable side effects. Here, I aim to identify mechanisms by which endocannabinoids regulate reward seeking through interactions with dopamine system function to identify precise neuronal targets for future cannabinoid-based therapies. I will test the hypothesis that synthesis of the endocannabinoid 2-arachidonoylglycerol by dopamine neurons is required for dopamine neurons to encode the incentive value of reward-predicting cues and motivate reward seeking. This work will employ two cutting-edge techniques, fast-scan cyclic voltammetry and optogenetics, paired with conditional and inducible mutagenesis to selectively target the enzyme responsible for 2-arachidonoylglycerol synthesis within dopamine neurons. Our ability to target dopamine neuron function in real-time during behavior and manipulate specific elements of the endocannabinoid system will provide novel information concerning how endocannabinoid signaling motivates reward seeking, potentially enabling the development of more targeted pharmacotherapies.

项目摘要/摘要支持药物滥用和肥胖的不适应形式的奖励寻求给个人造成了巨大的损失和经济健康。越来越多的临床前和临床工作表明，内源性大麻素制度有力地规范了奖励的激励影响。在药物治疗靶向的同时内源性大麻素功能对治疗寻求奖赏障碍是有效的，这一途径受到了阻碍由于非特定的药物作用和不可接受的副作用。在这里，我的目标是确定通过哪些机制内源性大麻素通过与多巴胺系统功能相互作用调节奖赏寻求未来大麻类药物治疗的精确神经元靶点。我将测试这一假设，即合成的多巴胺神经元需要内源性大麻素2-花生酰甘油来编码奖励的激励价值--预测线索和激励奖励寻求。这项工作将使用两个尖端的快速扫描循环伏安和光遗传学技术，结合条件诱变和诱变选择性地靶向多巴胺神经元内负责合成2-花生四烯基甘油的酶。我们的能够在行为过程中实时定位多巴胺神经元的功能，并操纵内源性大麻素系统将提供有关内源性大麻素信号如何激励的新信息寻求奖励，潜在地使更有针对性的药物疗法的开发成为可能。