REGULATION OF MESOLIMBIC DOPAMINE BY ENDOGENOUS COMPOUND

内源性化合物对中脑边缘多巴胺的调节

• 批准号: 2851839
• 负责人: Peter W Kalivas
• 金额: $ 21.86万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2851839
• 关键词: behavioral /social science research tag; brain mapping; chordate locomotion; dopamine; enkephalins; experimental brain lesion; gamma aminobutyrate; glutamates; laboratory rat; limbic system; memory; microdialysis; microinjections; motivation; motor cortex; motor neurons; neural information processing; neural transmission; neuroanatomy; neurochemistry; neuropharmacology; nucleus accumbens; psychomotor function; stereotaxic techniques

DESCRIPTION (Adapted from the Applicant's abstract) This proposal will characterize a portion of the neural circuitry responsible for translating motivationally relevant stimuli into adaptive motor responses. This circuit is termed the motive circuit and contains interconnected brain nuclei which interface between traditional limbic and motor nuclei, including the, nucleus accumbens, ventral tegmental area, ventral pallidum, mediodorsal thalamus and prefrontal cortex. The flow of information through this circuit will be characterized in the context of two behavioral measures, locomotor hyperactivity and spatial delayed alternation in a T-maze. Four neurotransmitter systems will be evaluated, including dopamine, glutamate, GABA and enkephalin using microinjection of transmitter analogues, microdialysis and double labeling techniques to chemically code the anatomical interconnections. In addition, recent studies reveal neuroadaptations within the functional organization of the motive circuit subsequent to dopamine depletion in the nucleus accumbens, and studies are proposed to investigate the basis of this neuroplasticity. Pathophysiological alterations within the motive circuit have been implicated in the etiology and expression of neuropsychiatric disorders, notably in schizophrenia. The information generated by this proposal will identify new opportunities for the pharmacological manipulation of the motive circuit and will provide neurochemical and functional maps that will be useful in evaluating anatomical selectivity in the actions of psychotherapeutic agents. Also, the functional maps generated by this research will have utility in discerning and correlating patterns of change revealed in future brain imaging studies of psychiatric patients and their responses to environmental or pharmacological challenges.

描述（改编自申请人的摘要）本提案将 表征负责翻译的神经回路的一部分， 动机相关刺激转化为适应性运动反应。该电路 被称为运动回路，包含相互连接的脑核团， 传统的边缘核和运动核之间的界面，包括，核 腹侧苍白球、背内侧丘脑和腹侧被盖区 前额皮质通过这个电路的信息流将是 以两种行为测量为特征，运动 活动过度和空间延迟交替。四 将评估神经递质系统，包括多巴胺、谷氨酸、GABA 和脑啡肽，使用微量注射递质类似物，微透析， 双标记技术来化学编码解剖学互连。 此外，最近的研究表明，神经适应的功能， 组织的运动电路后，多巴胺耗竭，在 的核，并提出研究调查的基础上， 神经可塑性运动回路中的病理生理变化 与神经精神疾病的病因学和表现有关， 尤其是精神分裂症。本提案产生的信息将 为动机的药理学操作确定新的机会 电路，并将提供神经化学和功能地图，这将是有用的 在评估心理治疗作用中的解剖选择性时， 剂.此外，本研究所产生的功能图将具有实用性 在辨别和关联未来大脑中的变化模式时， 精神病患者的影像学研究及其对环境或 药理学挑战