Accumbal Activity Under Drug and Non-Drug Rewarded Tasks

描述(申请人提供)：可卡因成瘾者持续寻求和服用可卡因，并且无法抑制这些行为，尽管知道有不良后果。可卡因成瘾的具体神经机制仍不清楚，需要进一步研究。拟议的研究计划探索了一个新的假设，潜在地解释了伏隔核和相关回路中的特定适应是如何导致成瘾的。简而言之，该假说观察到，大多数伏隔神经元在可卡因暴露时受到抑制，并在反复暴露可卡因时变得慢性低活动。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，因此不会在反复暴露时变得慢性低活动。通过这种方式，这些神经元获得了对伏隔信号的增强影响，从而促进了进一步的可卡因寻找和服用。使用慢性电生理技术，本提案旨在测试这一假说的几个预测，同时也与目前关于伏隔功能的文献相结合并做出贡献。相关性：可卡因成瘾给我们的社会带来了巨大的经济、社会和公共卫生方面的代价，也给上瘾的个人及其家人和朋友带来了巨大的个人代价。这组实验将研究可卡因如何改变大脑奖赏回路中神经元的反应。对可卡因行为的更全面了解最终可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.