Cue-triggered Reward Seeking

提示触发的奖励寻求

基本信息

批准号：
9306471
负责人：
Kent C. Berridge
金额：
$ 36.03万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9306471
关键词：
Abstinence Aftercare Amygdaloid structure Anatomy Animals Brain Cell Nucleus Cocaine Cues Development Distress Emotional Family Feeling Future Globus Pallidus Goals Habits Halorhodopsins Hypothalamic structure Incentives Intravenous Laboratories Lateral Life Mediating Motivation Nature Neurobiology Neurons Neurosciences Outcome Output Persons Pharmaceutical Preparations Physiological Pilot Projects Psychological reinforcement Recording of previous events Recruitment Activity Relapse Reporting Response to stimulus physiology Rewards Role Stimulus Stress Structure Sucrose Sum Testing Time Ventral Tegmental Area Withdrawal Withdrawal Symptom addiction base brain circuitry career cost drug addict drug of abuse drug reward experience experimental study improved incentive salience interest loss of function operation optogenetics pleasure tool

项目摘要

Addictive urges often have several specific motivation features: the motivational urge is a) highly intense, b) narrowly focused on the addicted target (e.g., drugs), and c) sometimes seemingly `irrational', in the sense of not being explainable by past or expected reinforcement values even for the addicts themselves. For example, relapse can occur even when the addict is no longer in withdrawal, and knows from past experience that the available drug is not very pleasant, and does not expect the future drug to be very pleasant. Here we use optogenetic tools to study brain mechanisms that generate these powerful motivation features. This proposal takes advantage of our recent discovery that optogenetic stimulation of amygdala-related circuitry creates powerful motivational urges for cocaine or sucrose rewards that are a) narrowly focused, b) highly intense, and c) irrational in the sense of exceeding the sum of component reinforcements. This manipulation recreates in the laboratory the same features of motivation that need understanding in addiction. Experiment 1 will identify the crucial anatomical site within amygdala, and identify the particular neuron subpopulations, responsible for generating this intense yet narrow urge for a particular reward, even at the expense of other rewards. Experiment 2 will examine larger brain interactions of the amygdala with mesolimbic circuits, to identify the responsible larger brain circuitry. Experiment 3 will examine how drug-induced mesolimbic sensitization interacts with this circuitry to exacerbate these three features of addictive-like motivation. Altogether, these studies will help clarify how brain mechanisms generate excessive yet narrow, and even irrational, urges (similar to the addictive urges that make drug addicts relapse).

上瘾的冲动通常有几个特定的动机特征： a) 高度强烈，b) 狭隘地集中于成瘾目标（例如毒品），以及 c) 有时看似“非理性”，即无法用过去或过去来解释即使对于成瘾者本身来说，预期的强化值也是如此。例如，复发可以即使成瘾者不再戒断并且从过去的经验中知道，也会发生现有的药物不是很令人愉快，并且预计未来的药物不会是非常愉快。在这里，我们使用光遗传学工具来研究产生这些强大的大脑机制动机特征。该提案利用了我们最近的发现：杏仁核相关电路的光遗传学刺激产生强大的动机对可卡因或蔗糖奖励的渴望是 a) 狭隘的，b) 高度强烈的，以及 c) 超出构件强化总和的意义上的非理性。这操纵在实验室中重现了与需要的动机相同的特征成瘾中的理解。实验 1 将识别杏仁核内的关键解剖部位，并识别特定的神经元亚群，负责产生这种强烈而狭窄的强烈要求某种特定的奖励，甚至不惜牺牲其他奖励。实验2将检查杏仁核与中脑边缘回路的更大大脑相互作用，以确定负责的较大大脑回路。实验3将检验药物如何诱导中脑边缘敏化与该电路相互作用，加剧了这三个特征令人上瘾的动机。总而言之，这些研究将有助于阐明大脑如何机制会产生过度但狭隘甚至非理性的冲动（类似于使吸毒成瘾者复发的成瘾冲动）。