Interaction Between PACAP and Stress-Induced Behavior

PACAP 与压力诱发行为之间的相互作用

• 批准号: 6477761
• 负责人: GABOR LEGRADI
• 金额: $ 0.66万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2002-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6477761
• 关键词: amygdala; behavior test; behavioral /social science research tag; brain mapping; dosage; hypothalamus; injection /infusion; laboratory rat; neuropeptide receptor; neuropeptides; neuropharmacology; neuropsychology; open field behavior; restraint; startle reaction; stress

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.

描述（由申请人提供）：拟议实验的主要目标 在这个探索性/开发性 R21 应用中是确定是否 大脑中的垂体腺苷酸环化酶激活多肽（PACAP）可能 调解压力引起的行为表现。自此以来的过去十年里 PACAP 的发现，使人们对分子生物学有了很多了解， PACAP 的细胞作用和分布，但行为特征 这种潜在的重要肽仍然缺乏。 PACAP 具有广泛的、 但在大脑中观察到的浓度最高的独特分布 在下丘脑、扩展杏仁核和下脑干中， 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 其他我们假设 PACAP 的核心行动参与 应激反应的详细阐述以及 PACAP 可能起到增强作用 自然发生的压力诱发行为。在规定的期限内 提案中，我们计划探索 PACAP 的行为作用，特别是在 下丘脑室旁核（PVN）和中央核 杏仁核（CeA）。目标 1 将研究剂量反应和大脑 约束应激后应激后行为事件的部位特异性 以及旷场暴露或局部接触后的触觉惊吓反射 将 PACAP 显微注射到 PVN 或 CeA 中。目标 2 将重点关注可能的情况 内源性 PACAP 在 PVN 和杏仁核水平的作用，并将使用 选择性 PACAP 受体拮抗剂的局部显微注射。微分 减弱压力引起的行为 - 基于注射位置 站点和行为参数的类型 - 将用于确定站点 内源释放的 PACAP 在应激激活中的特定作用。这是 预计这些实验的数据将提供新的信息 关于 PACAP 中枢作用的一些显着大脑部位， 这将有助于更好地理解与压力相关的 失调。