Cue-triggered reward seeking

描述（由申请人提供）：戒毒者在面对与毒品有关的线索或环境时会遇到危险，因为这些情况会引发复发。同样，暴饮暴食往往是由食物相关奖励的暗示引发的。当个体处于脆弱状态时，暗示是特别有效的触发因素。这些建议旨在确定大脑状态，这些状态会导致容易受到线索触发的“渴望”奖励的影响。负责的大脑机制特别涉及边缘伏隔核和杏仁核。在这里，我们将研究这些大脑机制是如何将过度的激励显著性（“想要”）归因于特定的奖励线索的。在实验1中，将使用微注射激动剂药物和Fos羽流绘图工具来识别伏隔核和杏仁核中放大线索触发的“欲望”的神经机制。在实验2中，将通过同时进行多次显微注射来操纵伏隔核和杏仁核的结构，从而确定将伏隔核和杏仁核连接成一个合作系统的回路原理。在实验3中，先前的神经致敏和学习操作将有助于展示自然的“想要”机制是如何被药物和致敏篡夺的，从而导致成瘾奖励比其他奖励更“想要”。这些研究将有助于阐明导致成瘾者过度“想要”毒品和暴饮暴食者过度“想要”食物奖励的大脑和心理机制。公共卫生相关性：药物成瘾和暴饮暴食障碍的一个主要问题是，遇到成瘾奖励的线索（即使在长时间的戒断之后），复发的持续危险。一种大脑机制被假设为导致线索触发的复发，即大脑系统产生正常的“想要”奖励的激励敏化。这里提出的研究将有助于揭示暗示引发复发的大脑机制，并将阐明成瘾和饮食失调是如何产生强迫性“欲望”的。

DESCRIPTION (provided by applicant): Recovering drug addicts encounter danger when faced with drug-related cues or contexts, because those situations can trigger relapse. Similarly, bouts of binge eating are often triggered by cues for food relevant rewards. Cues are especially potent triggers when individuals are in vulnerable states. These proposal aims to identify the brain states that cause vulnerability to cue-triggered 'wanting' of reward. The responsible brain mechanisms particularly involve the limbic nucleus accumbens and amygdala. Here we will study how these brain mechanisms cause excessive incentive salience ('wanting') to be attributed to particular reward cues. In experiment 1, microinjections of agonist drugs and a Fos plume mapping tool will be used to identify the neural mechanisms in nucleus accumbens and amygdala that magnify cue-triggered 'wanting'. In experiment 2, the circuit principles that join together the nucleus accumbens and amygdala into a cooperative system will be identified by manipulating the structures with multiple simultaneous microinjections. In experiment 3, prior neural sensitization and learning manipulations will help show how natural 'wanting' mechanisms are usurped by drugs and sensitization to cause an addicted reward to be 'wanted' more than other rewards. These studies will help clarify the brain and psychological mechanisms that cause addicts to excessively 'want' drug and binge eaters to excessively 'want' food rewards. PUBLIC HEALTH RELEVANCE: A primary problem in drug addiction and binge eating disorders is the continuing danger for relapse posed by encounters with cues for the addicted reward (even after long periods of abstinence). A brain mechanism has been hypothesized to cause cue-triggered relapse, namely incentive sensitization of brain systems that generate normal 'wanting' for rewards. The studies proposed here will help reveal those brain mechanisms underlying cue-triggered relapse, and will shed light on how compulsive 'wants' are produced in addiction and in eating disorders.