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：
10279277
负责人：
THOMAS C JHOU
金额：
$ 57.36万
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 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10279277
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 aversive conditioning cocaine exposure dopaminergic neuron drinking drug of abuse experience experimental study glutamatergic signaling individual variation inhibitor/antagonist 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：滥用药物（例如可卡因）会产生有益效果，这一点已得到广泛研究。这些也会产生令人厌恶的影响，尽管它们强烈影响寻求药物，并表现出很大的个体差异，导致个体成瘾的差异我们发现对可卡因的厌恶反应主要取决于血清素和谷氨酸。嘴内侧被盖核 (RMTg) 中的信号传导，是中脑多巴胺神经元的主要传入神经元。该提案研究了这些受体驱动神经激活和厌恶的细胞机制条件作用，以及为什么这些反应在某些人身上比其他人发生得更强烈，总体目标是确定新的潜在治疗靶点以调节药物寻求和治疗瘾。