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: 6711721
• 负责人: GABOR LEGRADI
• 金额: $ 14.38万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 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 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6711721
• 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）：拟定实验的主要目标 在本探索性/开发性R21应用程序中， 脑中的垂体腺苷酸环化酶激活多肽（PACAP）可能 介导压力诱导的行为表现。在过去的十年中， PACAP的发现，使人们对分子生物学有了更多的了解， 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拥有广泛的， 但在大脑中的独特分布， 在下丘脑、杏仁核和脑干下部， 与神经内分泌和行为过程高度相关 压力的表现。根据我们工作的初步证据， 其他人，我们假设，中央行动的PACAP参与， 阐述应激反应和PACAP可能起到增强 自然发生的压力诱发的行为在期限内， 建议，我们计划探讨行为的作用，PACAP特别是在 下丘脑室旁核（PVN）和中央核 杏仁核（CeA）。目的1将研究剂量反应和脑 束缚应激后行为事件的位点特异性 以及开放视野暴露或局部刺激后的触觉惊吓反射 将PACAP微量注射到PVN或CeA中。目标2将侧重于可能的 内源性PACAP在PVN和杏仁核水平的作用，并将使用 局部微量注射选择性PACAP受体拮抗剂。微分 应力诱导行为的钝化-基于注射位置 站点和行为参数的类型-将用于确定站点 内源性释放的PACAP在应激激活中的特殊作用。是 预计这些实验的数据将提供新的信息， 关于PACAP中枢作用的一些显著脑部位， 这将有助于更好地理解与压力相关的 紊乱

项目成果

Microinfusion of pituitary adenylate cyclase-activating polypeptide into the central nucleus of amygdala of the rat produces a shift from an active to passive mode of coping in the shock-probe fear/defensive burying test.

• DOI: 10.1155/2007/79102
• 发表时间: 2007
• 期刊: Neural plasticity
• 影响因子: 3.1
• 作者: Legradi G;Das M;Giunta B;Hirani K;Mitchell EA;Diamond DM
• 通讯作者: Diamond DM