Accumbal Activity Under Drug and Non-Drug Rewarded Tasks

描述（由申请人提供）：可卡因成瘾者持续寻求和服用可卡因，尽管知道不良后果，但无法抑制这些行为。可卡因成瘾的具体神经机制尚不清楚，需要进一步研究。拟议中的研究计划探索了一个新的假设，该假设可能解释了神经核和相关电路中的特定适应如何导致成瘾。简单地说，该假说观察到大多数延髓神经元在可卡因暴露下受到抑制，并且随着重复可卡因暴露而变得慢性活动减退。然而，在自我给药期间对可卡因相关事件（即：线索，杠杆按压）做出反应的神经元组在可卡因暴露期间保持其放电率，因此不会随着重复暴露而变得慢性活动减退。通过这种方式，这些神经元获得了对可卡因信号的增强影响，这有助于进一步寻找和服用可卡因。使用慢性电生理技术，本建议的目的是测试这一假设的几个预测，同时也整合和促进目前的身体的文献对脑功能。相关性：可卡因成瘾给我们的社会带来了巨大的经济、社会和公共卫生损失，也给成瘾者、他们的家人和朋友带来了巨大的个人损失。目前的一系列实验将研究可卡因如何改变大脑奖励回路中神经元的反应。对可卡因作用的更全面了解最终有望有助于开发有效的可卡因成瘾治疗方法。

DESCRIPTION (provided by applicant): Cocaine addicted individuals persistently seek and take cocaine, and have an inability to inhibit these behaviors, despite the knowledge of adverse consequences. The specific neural mechanisms that underlie cocaine addiction are still unclear, and require further research. The proposed research plan explores a new hypothesis that potentially explains how specific adaptations in the nucleus accumbens, and related circuitry, result in addiction. Briefly, the hypothesis observes that most accumbal neurons are inhibited under cocaine exposure, and become chronically hypoactive with repeated cocaine exposure. However, the set of neurons that respond to cocaine-related events (ie: cues, lever presses) during a self-administration session maintain their firing rates during cocaine exposure, and therefore do not become chronically hypoactive with repeated exposure. In this way, these neurons gain an enhanced influence over accumbal signaling, which facilitates further cocaine-seeking and taking. Using chronic electrophysiological techniques, the present proposal is designed to test several predictions of this hypothesis, while also integrating with and contributing to the present body of literature on accumbal function. Relevance: Cocaine addiction exacts enormous financial, social, and public health tolls on our society, as well as large personal tolls on the addicted individuals, their families, and their friends. The present set of experiments will examine how cocaine alters the responses of neurons in the brain's reward circuits. A more complete understanding of the actions of cocaine is ultimately expected to contribute to the development of effective treatments for cocaine addiction.