Neural Mechanisms of Individual Differences in Cocaine Avoidance

可卡因回避个体差异的神经机制

基本信息

批准号：
10453809
负责人：
THOMAS C JHOU
金额：
$ 45.74万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10453809
关键词：
AMPA Receptors Addictive Behavior Agonist Alcohol consumption Alcohols Anatomy Automobile Driving Behavioral Biological Calcium Cell Nucleus Cocaine Data Dependence Disulfiram Enzymes Ethanol Metabolism Exhibits Glutamates Habits Individual Individual Differences Learning Lesion Mediation Midbrain structure Molecular Molecular Target Motivation Neurons Nicotine Nicotinic Receptors PTEN gene Peptides Permeability Pharmaceutical Preparations Phase Phosphoric Monoester Hydrolases Play Publishing Rattus Receptor Signaling Regulation Rewards Role Serotonin Serotonin Receptor 5-HT2C Signal Transduction Smoking Source Specificity Testing Therapeutic Variant Work addiction addiction liability aversive conditioning cocaine exposure dopaminergic neuron drinking drug of abuse experience experimental study glutamatergic signaling individual variation inhibitor neuromechanism new therapeutic target non-drug novel optogenetics protective effect receptor receptor function relating to nervous system response targeted treatment therapeutic target therapeutically effective

项目摘要

Abstract: Drugs of abuse, such as cocaine, produce rewarding effects that have been extensively investigated. However, these drugs also produce aversive effects that are far less understood, even though they strongly influence drug‐seeking, and exhibit large individual variability that contributes to differences in individual addiction propensity. We found that aversive responses to cocaine depend critically on serotonin and glutamate signaling in the rostromedial tegmental nucleus (RMTg), a major afferent to midbrain dopamine neurons. This proposal examines cellular mechanisms by which these receptors drive neural activation and aversive conditioning, and why these responses occur much more strongly in some individuals than others, with an overall aim of identifying novel potential therapeutic targets for regulating drug‐seeking and treating addiction.

抽象的：可卡因等滥用药物会产生经过广泛研究的奖励作用。然而，这些药物还会产生厌恶作用，尽管它们强烈影响寻求毒品，并暴露了巨大的个人变异性，这导致了个人成瘾的差异倾向。我们发现，对可卡因的厌恶反应严重取决于5-羟色胺和谷氨酸鼻膜细饰核（RMTG）中的信号传导，这是中脑多巴胺神经元的主要传入。这建议检查这些受体驱动神经激活和厌恶性的细胞机制调理，以及为什么在某些人中比其他人更强烈地发生这些反应，而有一个确定用于控制毒品和治疗的新型潜在治疗靶标的总体目的瘾。