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：
9438372
负责人：
Daniel Patrick Covey
金额：
$ 6.3万
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 2019-02-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9438372
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.

项目概要/摘要支持药物滥用和肥胖的不适应奖励寻求形式对个人造成巨大损失和经济健康。越来越多的临床前和临床工作表明，内源性大麻素系统有力地调节了奖励的激励影响。虽然药物治疗针对内源性大麻素功能治疗奖励寻求障碍是有效的，但这种方法已受到阻碍由于非特异性药物作用和不可接受的副作用。在这里，我的目的是确定机制内源性大麻素通过与多巴胺系统功能相互作用来调节奖励寻求，以识别未来基于大麻素的疗法的精确神经元靶点。我将检验以下假设：多巴胺神经元需要内源性大麻素2-花生四烯酰甘油来编码奖励预测线索的激励价值并激发奖励寻求。这项工作将采用两位尖端技术技术，快速扫描循环伏安法和光遗传学，与条件和诱导诱变相结合选择性地靶向多巴胺神经元内负责 2-花生四烯酰甘油合成的酶。我们的在行为过程中实时定位多巴胺神经元功能并操纵特定元素的能力内源性大麻素系统将提供有关内源性大麻素信号传导如何激发的新信息寻求奖励，可能有助于开发更有针对性的药物疗法。