Interaction Between PACAP and Stress-Induced Behavior

描述(由申请人提供)：拟议实验的主要目标 在此探索性/开发性R21应用程序中，确定 脑组织中的垂体腺苷酸环化酶激活多肽 调节应激诱导的行为表现。在过去的十年里 PACAP的发现，人们已经了解了很多关于分子生物学的知识， PACAP的细胞作用和分布，但其行为特征 这种潜在的重要多肽仍然缺乏。PACAP有一个广泛的， 然而，在观察到的最高浓度的大脑中却有独特的分布 在下丘脑、延伸的杏仁核和下部脑干，这些区域是 与神经内分泌和行为的处理高度相关 压力的表现。根据我们工作的初步证据和 其他的我们假设PACAP的中心行动参与了 应激反应的阐述以及PACAP可能起到增强作用 自然发生的应激诱导行为。在规定的期限内 提案中，我们计划专门探讨PACAP在 下丘脑室旁核(PVN)和丘脑中央核 杏仁核(CEA)。目标1将研究剂量反应和大脑 束缚应激后应激后行为事件的部位特异性 以及开阔视野暴露或局部触觉惊吓反射 PVN或CEA内微量注射PACAP。目标2将专注于可能的 内源性PACAP在下丘脑室旁核和杏仁核水平的作用 局部微量注射选择性PACAP受体拮抗剂。差动 应激诱导行为的钝化-基于注射的位置 站点和行为参数的类型-将用于确定站点 内源性释放的PACAP在应激激活中的特殊作用。它是 预计来自这些实验的数据将提供新的信息 关于PACAP中枢活动的一些显著脑部位， 这将适用于更好地理解与压力相关的 精神错乱。

DESCRIPTION (provided by applicant): The main goal of the proposed experiments in this Exploratory/Developmental R21 application is to determine whether pituitary adenylate cyclase-activating polypeptide (PACAP) in the brain may mediate stress-induced behavioral manifestations. During the past decade since the discovery of PACAP, much has been learned about the molecular biology, cellular action and distribution of PACAP, but behavioral characterization of this potentially important peptide is still lacking. PACAP has a widespread, yet unique distribution in the brain with the highest concentrations observed in the hypothalamus, extended amygdala and lower brainstem, regions that are highly relevant for the processing of neuroendocrine and behavioral manifestations of stress. Based on preliminary evidence from our work and others we hypothesize that the central actions of PACAP participate in the elaboration of the stress response and that PACAP may act to potentiate naturally-occurring stress-induced behaviors. Within the time limit of the proposal, we plan to explore the behavioral role of PACAP specifically in the hypothalamic paraventricular nucleus (PVN) and the central nucleus of the amygdala (CeA). Aim 1 will investigate the dose-response and brain site-specificity of post-stress behavioral events following restraint stress and open field exposure or the tactile startle reflex following local microinjections of PACAP into the PVN or CeA. Aim 2 will focus on the possible role of endogenous PACAP at the level of the PVN and amygdala and will use local microinjections of a selective PACAP receptor antagonist. Differential blunting of stress-induced behaviors - based on the location of the injection site and the type of behavioral parameter - will be used to determine the site specific role of endogenously released PACAP in stress activation. It is anticipated that data from these experiments will provide novel information regarding some of the salient brain sites for the central actions of PACAP, which will be applicable toward a better understanding of stress-related disorders.