FUNCTIONAL PROPERTIES OF VTA NEURONS

VTA 神经元的功能特性

• 批准号: 2468015
• 负责人: ANN E KOSOBUD
• 金额: $ 9.17万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2468015
• 关键词: anesthesia; apomorphine; behavioral /social science research tag; conditioning; dopamine; fentanyl; laboratory rat; limbic system; neural information processing; neurons; neuropharmacology; preference; psychopharmacology

DESCRIPTION: (Applicant's Abstract) The development of effective strategies for the prevention and treatment of drug abuse requires a better understanding of the properties that give drugs their power to control behavior. The mesocorticolimbic dopamine (MCL DA) system, composed of the ventral segmental area (VTA) and its targets, appears to mediate natural goal-directed behavior, including feeding and sexual behavior. The addictive properties of drugs of abuse appear to arise through their interaction with the MCL DA system. Thus, all drugs of abuse (cocaine, amphetamine, heroin, ethanol, nicotine, etc.) share a common property of enhancing MCL DA release; blockade of DA transmission disrupts drug self-administration. In the proposed experiments, the activity of VTA neurons will be recorded in awake rats engaged in goal-directed behaviors, in order to evaluate the specific role that VTA neurons play in natural motivated behavior. Establishing the role of these neurons in normal behavior is a necessary first step to understanding their role in the pathology of drug addiction. Consistent with the goal of studying normal behavior, these experiments use chronically implanted microwire electrodes which allow long-term stable recording in awake, behaving rats. In Aim 1, recordings will be obtained during 1) a free-choice novelty task; 2) classical conditioning of a tone-sucrose solution association and 3) acquisition and performance of lever-pressing for sucrose solutions. Because at least 3 classes of neuron (DA and non-DA projecting neurons, and interneurons) are known to be present in the VTA, Aim 2 includes four experiments aimed at identification and characterization of the neuron recordings. Experiments 1 and 2 will survey the basic electrophysiological properties of these neurons, and determine their response to two drug probes, apomorphine (which inhibits DA neurons through actions at autoreceptors) and alfentanil (a short-acting ,mu-opiate agonist which should, like morphine, activate DA neurons). Experiment 3 is a direct comparison of neural activity in the awake and anesthetized rat, establishing a link between the vast literature describing VTA DA cells in anesthetized rats and the present studies. Experiment 4 adds antidromic stimulation as a means of identifying the targets of the recorded neurons. The proposed experiments will provide a better understanding of the functional relationship among the various neuron subtypes in the VTA, and the contribution of these neurons to motivated behavior.

描述：（申请人的摘要） 制定预防和治疗的有效策略 药物滥用需要更好地了解给药的特性 他们控制行为的力量。 中皮质糖多巴胺（MCL DA） 系统，由腹侧分段区域（VTA）及其目标组成 似乎可以调解自然目标指导的行为，包括喂养和 性行为。 滥用毒品的上瘾特性似乎出现了 通过与MCL DA系统的互动。 因此，所有滥用药物 （可卡因，苯丙胺，海洛因，乙醇，尼古丁等）共享 增强MCL DA版本的财产；封锁DA传输中断 药物自我管理。 在拟议的实验中，VTA的活性 神经元将记录在从事目标指导行为的清醒老鼠中 为了评估VTA神经元在自然中扮演的特定作用 动机行为。 确定这些神经元在正常中的作用 行为是了解他们在 药物成瘾的病理学。 与研究正常的目标一致 行为，这些实验使用长期植入的微波电极 这允许在清醒中长期稳定记录，行为大鼠。 在AIM 1中， 在1）自由选择的新颖任务期间将获得录音； 2） 音调 - 核溶液关联的经典条件和3） 蔗糖解决方案的杠杆压力的采集和性能。 因为至少3类神经元（DA和非DA预测神经元，以及 已知中间神经元存在于VTA中，AIM 2包括四个 旨在识别和表征神经元的实验 录音。 实验1和2将调查基本电生理学 这些神经元的特性，并确定它们对两种药物的反应 探针，丙氨酸（通过在 自身受体）和阿尔芬太尼（一种短效，摄影作用者，该激动剂 像吗啡一样，应该激活DA神经元）。 实验3是直接的 在清醒和麻醉大鼠中的神经活动的比较， 在描述VTA DA细胞的大量文献之间建立联系 麻醉大鼠和目前的研究。 实验4添加了抗原 刺激是识别记录神经元目标的一种手段。 提出的实验将为您更好地理解 VTA中各种神经元亚型之间的功能关系， 这些神经元对动机行为的贡献。