REGULATION OF BRAIN NORADRENERGIC NEUROTRANSMISSION

大脑去甲肾上腺素能神经传递的调节

• 批准号: 6330256
• 负责人: ERIC A STONE
• 金额: $ 25.98万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6330256
• 关键词: alpha adrenergic receptor; behavioral /social science research tag; brain electrical activity; corticosterone; cyclic AMP; electrostimulus; hormone regulation /control mechanism; laboratory rat; microdialysis; neural transmission; norepinephrine; psychopharmacology; receptor sensitivity; stress

DESCRIPTION (applicant's abstract): The present grant is a revision of a previous proposal, MH45265, whose aim was to elucidate the role of central alpha-l noradrenergic function in stress-induced behavioral dysfunction. The proposal is focussed on a proposed neurobiological pathway by which stress produces behavioral inactivity via a corticosterone-induced desensitization of behaviorally activating brain alpha-1 adrenergic receptors. The proposed studies will further elucidate this pathway by determining: 1) the subtype of brain alpha-1 receptor (1A, 1B or ID) that mediates behavioral activation and whether it is desensitized by stress and corticosterone as preliminary data indicate; 2) the brain region within which it acts to stimulate behavioral activity; 3) the role of endogenous corticosterone and individual corticosteroid receptors in its desensitization by stress; and 4) the role of changes in the density and coupling of this alpha-1 receptor in the mechanism of the desensitization. The proposed studies will yield important clues on the pathophysiology of inactive behavioral states occurring in several psychiatric and stress related disorders and will stimulate clinical research into possible alterations in brain alpha-l receptors that may sensitize individuals to stress-induced behavioral impairment.

描述(申请人摘要)：本次资助是对一项 之前的提案，MH45265，其目的是阐明中央 阿尔法-L去甲肾上腺素在应激性行为障碍中的作用。这个 提案的重点是提出了一种神经生物学途径，应激通过这种途径 通过皮质酮诱导的脱敏产生行为静止 从行为上激活脑α-1肾上腺素能受体。建议数 研究将进一步阐明这一途径，确定：1)亚型 脑α-1受体(1A、1B或ID)，介导行为激活和 应激和皮质酮是否脱敏作为初步数据 指示；2)大脑中刺激行为的区域 活性；3)内源性皮质酮和个体的作用 皮质类固醇受体在应激脱敏中的作用 这种α-1受体密度和偶联的变化在机制中的作用 脱敏的原因。拟议的研究将产生关于 几种精神疾病患者不活动行为状态的病理生理学研究 和压力相关的障碍，并将刺激临床研究 脑内α-L受体的改变可能使个体对 应激导致的行为障碍。