Neural Mechanism by which Punishment Modulates Drug-Seeking

惩罚调节药物寻求的神经机制

• 批准号: 8543692
• 负责人: THOMAS C JHOU
• 金额: $ 17.7万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8543692
• 关键词: Ablation; Addictive Behavior; Affective; Animals; Anxiety; Area; Automobile Driving; Aversive Stimulus; Behavior; Behavior Disorders; Brain; Brain region; Cell Nucleus; Characteristics; Cocaine; Cocaine Dependence; Cognitive; Data; Educational process of instructing; Elements; Employee Strikes; Fiber; Food; Fright; Future; Human; Impairment; Individual; Individual Differences; Learning; Lesion; Midbrain structure; Modeling; Neurons; Outcome; Pathology; Pattern; Pharmaceutical Preparations; Phenotype; Primates; Punishment; Rattus; Reporting; Resistance; Rewards; Role; Shock; Signal Transduction; Stimulus; Structure; Testing; Time; Toxic effect; Variant; Withdrawal; abstracting; addiction; adverse outcome; awake; clinically relevant; cost; design; dopaminergic neuron; drug addict; drug reward; endophenotype; learned behavior; neuromechanism; optogenetics; social

DESCRIPTION (provided by applicant): One of the defining features of addictive behavior is its persistence despite potentially severe adverse outcomes. To further understand why addicts fail to learn from negative outcomes, we propose to explore the role of a newly identified brain region, the rostromedial tegmental nucleus (RMTg), which we and others have recently shown to encode negative reward prediction errors, and to be critically involved in a variety of aversive behaviors. We hypothesize that impairment of this structure leads to an addiction phenotype in which animals persistently seek outcomes despite aversive outcomes. We propose two aims, the first of which is designed to better understand the basic mechanisms by which the RMTg contributes to learning about negative outcomes. Our second aim is more translational, exploring the role of the RMTg in cocaine-seeking under punishment, as well as its contribution to individual variation in propensity to develop addictive behaviors.

描述（由申请人提供）：成瘾行为的定义特征之一是尽管可能产生严重的不良后果，但其持续存在。为了进一步理解为什么成瘾者无法从负面结果中学习，我们建议探索新发现的大脑区域，即嘴内侧被盖核（RMTg）的作用，我们和其他人最近已经证明该区域编码负面奖励预测错误，并与各种厌恶行为密切相关 行为。我们假设这种结构的损伤会导致成瘾表型，其中动物尽管厌恶结果却坚持不懈地寻求结果。我们提出两个目标，第一个目标是为了更好地理解 RMTg 有助于了解负面结果的基本机制。我们的第二个目标更具转化性，探索 RMTg 在惩罚下寻求可卡因中的作用，以及它对发展成瘾行为倾向的个体差异的贡献。

项目成果

The rostromedial tegmental (RMTg) "brake" on dopamine and behavior: A decade of progress but also much unfinished work.

• DOI: 10.1016/j.neuropharm.2021.108763
• 发表时间: 2021-10-15
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Jhou TC

Pumping the brakes: rostromedial tegmental inhibition of compulsive cocaine seeking.

踩刹车：嘴内侧被盖抑制强迫性可卡因寻求。

• DOI: 10.1101/2023.10.04.560908
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Vento,PeterJ;Watson,JacobR;Pullmann,Dominika;Black,SamanthaL;Tomberlin,JensenS;Jhou,ThomasC
• 通讯作者: Jhou,ThomasC

Entopeduncular Nucleus Projections to the Lateral Habenula Contribute to Cocaine Avoidance.

内脚核投射到外侧缰核有助于避免可卡因。

• DOI: 10.1523/jneurosci.0708-20.2020
• 发表时间: 2021
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Li,Hao;Eid,Maya;Pullmann,Dominika;Chao,YingS;Thomas,AlenA;Jhou,ThomasC
• 通讯作者: Jhou,ThomasC