ALPHA-1 ADRENERGIC SYSTEM IN ACTIVITY AND DEPRESSION

描述（由申请人提供）：本提案是对先前资助MH 45265的修订，其目的是阐明抑郁症患者缺乏积极动机行为的神经生物学。该项目的目标是更精确地确定这些行为在这种疾病中是如何被破坏的。先前的研究表明，脑肾上腺素（EPI）和中枢α-1肾上腺素受体，这两者在先前的抑郁症研究中都被忽视，在动物的积极动机行为中起着关键作用，并被已知会诱导抑郁行为的压力源所改变。具体而言，这些研究提出了以下假设：脑EPI是行为激活α-1受体的内源性神经递质，并且这种“EPI/α-1系统”特别涉及积极动机行为，而不是消极动机行为。这些假设将在本提案中进行测试的神经药理学，行为，免疫组织化学和神经化学实验，将评估脑EPI的内源性兴奋剂的作用，这个系统和系统的作用，在各种积极的动机活动，包括自我刺激的外侧下丘脑，条件的方法和避免积极和消极的刺激，和努力的操作行为。这项研究可能会将EPI/alpha-1系统确定为抗抑郁和抗应激药物的新的重要靶点

DESCRIPTION (provided by applicant): The present proposal is a revision of a previous grant, MH45265, whose aim was to elucidate the neurobiology of positively motivated behaviors that are deficient in depressive illness. The goal of the project is to identify more precisely how these behaviors are disrupted during this disorder. Previous work on this grant has shown that brain epinephrine (EPI) and central alpha-1 adrenoceptors, both of which have been neglected in prior research on depression, play key roles in positively motivated behaviors in animals and are altered by stressors that are known to induce depressive behavior. Specifically these studies have suggested the hypotheses that brain EPI is the endogenous neurotransmitter for behaviorally activating alpha-1 receptors and that this "EPI/alpha-1 system" is specifically involved in positively- rather than negatively-motivated behaviors. These hypotheses will be tested in the present proposal by a combination of neuropharmacological, behavioral, immunohistochemical and neurochemical experiments that will assess the role of brain EPI as the endogenous stimulant of this system and the role of the system in various positively-motivated activities including self-stimulation of the lateral hypothalamus, conditioned approach and avoidance of positive and negative reinforcers, and effortful operant behavior. The research will likely identify the EPI/alpha-1 system as a new and important target for antidepressant and antistress medications