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: 6881305
• 负责人: DONALD JAY WOODWARD
• 金额: $ 16.63万
• 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 2005-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6881305
• 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）：中边区域包括 内侧和外侧前额叶皮层，伏隔核和腹侧 被认为是介导调节的神经信号的细分区域（VTA） 寻求奖励的行为。该研究计划将研究神经生理学 乙醇对奖励和学习功能的影响 中边系统。同时记录尖峰火车的高级方法 不同中比区域神经元大规模种群的活性 在许多几天中的许多会议上，都将应用于获取有关的信息 电路功能与乙醇在不同时间尺度上的作用有关。一个 最初的目的是确定中左右系统变化的进度 在获得乙醇自我管理的各个阶段的大鼠 从高分百分比逐渐淡化到高百分比乙醇的程序 专注。正常的长埃文斯大鼠将与近交P进行比较 （乙醇优先）从乙醇研究中心获得的大鼠 在美国印第安纳州。第二个目标将把响应的变化描述为语调线索 条件是提供有关在 喷口。第三个目标将研究中左右区域的神经元活性 操作响应的模式渐进式鼻子对乙醇的反应 在灭绝期间表现出持续反应的P大鼠中， 在酒精剥夺效果期间的反应增强。我们假设这一点 伏隔核将揭示最异构的反应 中央整合的特征；轨道额皮层会介导 品味和奖励估值t调节未来的行为选择选择，内侧 前额叶皮层将表现出反应选择的神经编码和VTA 多巴胺神经元将跟踪可预测未来奖励的提示信息。一个 统一的概念是乙醇将通过归纳产生广泛的影响 控制条件提示的僵硬性响应以获取奖励 寻求行为。