Cue-triggered Reward Seeking

提示触发的奖励寻求

• 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
• 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

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).

令人上瘾的冲动通常具有多种特定的动机特征：动机的冲动是 a）高度激烈，b）狭cosecon着上瘾的目标（例如，药物）和c） 有时似乎是“非理性的”，从过去或不可解释的意义上 预期的加强价值甚至对于吸毒者本身也是如此。例如，复发可以 即使瘾君子不再被撤回，也会从过去的经验中知道 可用的药物不是很愉快，并且不指望未来的药物是 非常愉快。 在这里，我们使用光遗传学工具来研究产生这些功能强大的大脑机制 动机功能。该建议利用了我们最近发现的 杏仁核相关电路的光遗传学刺激创造了强大的动机 敦促对可卡因或蔗糖奖励，这些奖励是a）狭窄专注的，b）高度强烈，并且 c）在超过组件增援总和的意义上是非理性的。这 操纵在实验室重新创建了需要的动机的功能 理解成瘾。 实验1将识别杏仁核内关键的解剖部位，并确定 特定的神经元亚群，负责产生这种强烈而狭窄的 敦促获得特定的奖励，即使以其他奖励为代价。实验2将 检查杏仁核与中侧电路的较大大脑相互作用，以识别 负责的较大的大脑电路。实验3将检查药物诱导的方式 中唇敏化与此电路相互作用，以加剧这三个特征 类似上瘾的动机。这些研究总之将有助于阐明大脑 机制会产生过度但狭窄甚至不合理的敦促（类似于 使吸毒者复发的上瘾的敦促）。