Accumbal Activity Under Drug and Non-Drug Rewarded Tasks

药物和非药物奖励任务下的累积活动

• 批准号: 7388876
• 负责人: Alexxai V Kravitz
• 金额: $ 3.15万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-01-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7388876
• 关键词: Acute; Affect; Animals; Behavior; Behavioral; Brain; Cell Nucleus; Cells; Chronic; Cocaine; Cocaine Dependence; Condition; Cues; Dependence; Development; Dose; Drug Addiction; Drug Exposure; Drug usage; Event; Exposure to; Family; Fire - disasters; Food; Friends; Genetic Predisposition to Disease; Globus Pallidus; Grant; Individual; Ingestion; Knowledge; Literature; Neurons; Nucleus Accumbens; Pharmaceutical Preparations; Phase; Population; Prefrontal Cortex; Public Health; Rate; Rattus; Relative (related person); Research; Resistance; Rewards; Risk; Schedule; Self Administration; Self-Administered; Sex Behavior; Signal Transduction; Societies; Structure; Sucrose; System; Techniques; Testing; Training; Water; Work; addiction; base; design; dopamine system; driving behavior; drug addict; drug development; drug reward; neuromechanism; research study; response; social

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.

描述（由申请人提供）：可卡因上瘾的人持续寻求和服用可卡因，尽管有不利的后果，但仍无法抑制这些行为。可卡因成瘾基础的特定神经机制仍不清楚，需要进一步研究。拟议的研究计划探讨了一个新的假设，该假设可能解释了伏隔核中的特定适应性以及相关的电路如何导致成瘾。简而言之，假设观察到大多数可卡因暴露抑制了大多数伏托神经元，并随着可卡因的反复暴露而长期发作。但是，对可卡因相关事件做出反应的神经元（即：提示，杠杆压力机）在自我管理过程中保持其在可卡因暴露期间的发射率，因此不会随着反复的暴露而长期发射。通过这种方式，这些神经元对伏托信号产生了增强的影响，这有助于进一步寻求可卡因和采取可卡因。使用慢性电生理技术，本提案旨在检验该假设的几个预测，同时还与当前有关伏托功能的文献进行了整合并促进。相关性：可卡因成瘾使我们的社会对我们的社会产生了巨大的财务，社会和公共卫生损失，以及对上瘾的个人，他们的家人和他们的朋友的大量个人损失。目前的实验集将研究可卡因如何改变大脑奖励电路中神经元的反应。最终，人们对可卡因的行为有更全面的了解有助于开发可卡因成瘾的有效治疗方法。