Cue-triggered Reward Seeking

成瘾冲动通常有几个具体的动机特征： a）高强度，B）狭窄地集中于成瘾目标（例如，药物），以及c） 有时似乎是“不合理的”，在这个意义上说，不能解释的过去或 甚至对成瘾者自己也是如此。例如，复发可以 即使成瘾者不再处于戒断状态，并且从过去的经验中知道， 现有的药物不是很令人愉快，并且不期望未来的药物 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 动机特征这项建议利用了我们最近的发现， 杏仁核相关回路的光遗传学刺激产生了强大的动机， 对可卡因或蔗糖奖励的渴望，a）集中范围狭窄，B）高度强烈， c）不合理的，即超过了各组成部分钢筋的总和。这 操纵在实验室中重新创造了同样的动机特征， 理解成瘾 实验1将确定杏仁核内的关键解剖部位，并确定 特定的神经元亚群，负责产生这种强烈而狭窄的 追求某种奖励，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的大脑相互作用，以确定 负责的更大的大脑回路。实验3将研究药物诱导的 中脑边缘敏化与该回路相互作用，以加剧这三个特征， 上瘾的动机总而言之，这些研究将有助于阐明大脑 机制产生过度但狭窄，甚至不合理的冲动（类似于 使吸毒者复吸的成瘾冲动）。

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).