REGULATION OF BRAIN NORADRENERGIC NEUROTRANSMISSION

描述（申请人的摘要）：本授权是一个修订 先前的建议，MH 45265，其目的是阐明中央的作用， α-l去甲肾上腺素能在应激诱导的行为功能障碍中的作用。的 一项提案的重点是一个拟议的神经生物学途径， 通过皮质酮诱导的脱敏产生行为不活动， 行为激活大脑α-1肾上腺素能受体。拟议 研究将进一步阐明这一途径，通过确定：1）亚型的 脑α-1受体（1A、1B或ID），介导行为激活， 作为初步数据， 表明; 2）大脑区域内，它的行为刺激 活动; 3）内源性皮质酮和个人的作用 皮质类固醇受体在应激脱敏中的作用 这种α-1受体的密度和偶联的变化， 的脱敏。拟议中的研究将提供关于 在几种精神疾病中发生的不活跃行为状态的病理生理学 和压力相关的疾病，并将刺激临床研究， 大脑α-l受体的改变可能使个体对 压力导致的行为障碍

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.