Accumbal Activity Under Drug and Non-Drug Rewarded Tasks

描述（由申请人提供）：可卡因成瘾个体持续寻求和服用可卡因，并且无法抑制这些行为，尽管知道不良后果。可卡因成瘾背后的具体神经机制尚不清楚，需要进一步研究。拟议的研究计划探索了一个新的假设，该假设可能解释伏隔核及其相关回路的特定适应如何导致成瘾。简而言之，该假说观察到大多数伏隔神经元在可卡因暴露下受到抑制，并在反复暴露可卡因时变得慢性活性低下。然而，在自我给药过程中，对可卡因相关事件（如线索、杠杆按压）做出反应的神经元在可卡因暴露期间保持其放电率，因此不会因反复暴露而变得慢性活性低下。通过这种方式，这些神经元增强了对伏隔核信号的影响，这有助于进一步寻找和服用可卡因。使用慢性电生理技术，本提案旨在测试这一假设的几个预测，同时也整合和贡献目前的伏隔神经功能文献。相关性：可卡因成瘾对我们的社会造成了巨大的经济、社会和公共卫生损失，对成瘾者、他们的家人和朋友也造成了巨大的个人损失。目前的一系列实验将检验可卡因如何改变大脑奖赏回路中神经元的反应。更全面地了解可卡因的作用，预计最终将有助于开发治疗可卡因成瘾的有效方法。

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.