Cue-triggered Reward Seeking

上瘾冲动通常有几个特定的动机特征：动机冲动是 A)高度紧张，b)狭隘地聚焦于上瘾的目标(例如，毒品)，以及c) 有时似乎是“非理性的”，意思是不能用过去或 预期的增援价值，甚至对瘾君子本身也是如此。例如，复发可以 即使吸毒者不再戒毒，并从过去的经验中得知，这种情况也会发生 现有的药物不是很令人愉快，而且预计未来的药物不会是 非常令人愉快。 在这里，我们使用光遗传工具来研究大脑机制，这些机制产生这些强大的 激励特征。这项提议利用了我们最近的发现 光遗传刺激杏仁核相关回路产生强大的动机 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)超出各组成部分增援之和的意义上的不合理。这 操控在实验室中重现了需要的相同的动机特征 对上瘾的理解。 实验1将确定杏仁核内的关键解剖位置，并确定 特定的神经元亚群，负责产生这种强烈而狭隘的 强烈要求特别的奖励，即使是以牺牲其他奖励为代价。实验2将 检查杏仁核与中脑边缘环路的较大大脑相互作用，以确定 负责的更大的大脑回路。实验3将考察药物如何诱导 中脑边缘敏感化与这一回路相互作用，加剧了 令人上瘾的动机。总之，这些研究将有助于阐明大脑是如何 机制产生过度但狭隘的、甚至是非理性的冲动(类似于 使吸毒者复发的上瘾冲动)。

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).