Ethanol and Neurophysiology of the Mesolimbic System

乙醇和中脑边缘系统的神经生理学

• 批准号: 6732000
• 负责人: DONALD JAY WOODWARD
• 金额: $ 36万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732000
• 关键词: behavioral /social science research tag; conditioning; cues; dopamine; electrodes; ethanol; laboratory rat; learning; limbic system; neurophysiology; neuropsychology; prefrontal lobe /cortex; reinforcer; self medication; substance abuse related behavior; taste; tegmentum

DESCRIPTION (provided by applicant): The mesolimbic regions including the medial and lateral prefrontal cortices, the nucleus accumbens, and ventral tegmental area (VTA) are thought to mediate the neural signals that regulate reward-seeking behaviors. This research program will study the neurophysiology of the influence of ethanol on the reward and learning functions of the mesolimbic system. Advanced methods for simultaneous recording of spike train activity of large scale populations of neurons in different mesolimbic regions over many sessions across days will be applied to obtain information on the circuit functions related to actions of ethanol over different time scales. An initial aim is to determine the progress of changes in the mesolimbic system in rats at all stages of acquisition of self-administration of ethanol by a procedure of fading from a high percent sucrose to a high percent ethanol concentration. Normal Long Evans rats will be compared with the inbred P (ethanol-preferring) rats to be obtained from the Center for Ethanol Research at U. Indiana. A second aim will characterize change in responses as tone cues are conditioned to provide information about the reward to be obtained at a spout. A third aim will study neuronal activity in mesolimbic regions on the pattern of operant responses progressive ratio nose poke responding for ethanol in the P rats that exhibit persistent responding during extinction, and enhanced responding during the Alcohol Deprivation Effect. We hypothesize that the nucleus accumbens will reveal the most heterogeneous responses characteristic of central integration; orbital frontal cortex will mediate taste and reward valuation t mediate future behavioral choice selection, medial prefrontal cortex will exhibit neural coding of response selection and that VTA dopamine neurons will track information of cues predictive of future reward. A unifying concept is that ethanol will exert widespread influences by induction of an inflexibility of control over conditioned cue responding for reward seeking behavior.

描述（由申请人提供）：中脑边缘区域，包括 内侧和外侧前额皮质、伏隔核和腹侧 被盖区（VTA）被认为介导调节神经信号 寻求奖励的行为。该研究计划将研究神经生理学 乙醇对大脑奖励和学习功能的影响 中脑边缘系统。同时记录尖峰序列的先进方法 不同中边缘区域大规模神经元群的活动 将应用跨天的多次会议来获取有关 与乙醇在不同时间尺度上的作用相关的电路功能。一个 最初的目标是确定中脑边缘系统变化的进展 大鼠在获得自我给予乙醇的各个阶段 从高百分比蔗糖褪色到高百分比乙醇的过程 专注。正常的 Long Evans 大鼠将与近交 P 大鼠进行比较 （偏好乙醇的）大鼠从乙醇研究中心获得 在美国印第安纳州。第二个目标是将响应的变化描述为语气提示 有条件提供有关在某个时间获得的奖励的信息 喷口。第三个目标是研究中脑边缘区域的神经元活动 操作反应模式 渐进比率 鼻子戳对乙醇的反应 在灭绝期间表现出持续反应的 P 大鼠中，以及 戒酒效应期间的反应增强。我们假设 伏隔核将揭示最异质的反应 集中集成的特点；眶额皮质将调解 品味和奖励评估调节未来的行为选择选择，中间 前额皮质将表现出反应选择的神经编码和 VTA 多巴胺神经元将跟踪预测未来奖励的线索信息。一个 统一的概念是乙醇将通过感应产生广泛的影响 对奖励反应的条件提示的控制不灵活 寻求行为。