NEUROTRANSMITTER AND OXYTOCIN RELEASE IN LACTATION

该应用程序是调查员发起的交互式的一个组件 研究项目补助金（IRPG）计划，其总体目标是 鉴定和表征中枢神经递质系统， 泌乳期大鼠催产素（OT）的分泌。此组件将 研究去甲肾上腺素（NE）和OT释放调节， 哺乳引起的下丘脑核团。以前的研究表明 NE和OT的核内释放的重要性， 连合/室旁核区，视上核 (SON)和终纹床核（BNST）在全身性OT 分泌物然而，刺激的释放和生理作用， 下丘脑NE和OT在哺乳诱导的OT分泌中的作用尚不清楚。为 例如，体细胞刺激在吸吮诱导的NE中的特定作用 下丘脑核团内的OT释放尚未研究。 此外，核内OT释放对全身OT的重要性 NE在核内OT释放中的作用尚不清楚。 最后，神经调节剂，例如组胺（His）， 血管紧张素II（AngII）和谷氨酸（GLU），它们改变CNS NE释放， 对哺乳诱导的OT分泌的影响尚未研究。主要 该项目的目标是：1）确定NE的重要性， 在全身OT分泌诱导的ACN/PVN、SON和BNST中的OT释放 2）确定神经调节剂是否改变核内NE 和/或由吮吸诱发的OT分泌。该项目将测试整体 假设l）吮吸刺激ACN/PVN、SON中的NE释放， BNST诱导核内OT释放和外周OT分泌 哺乳期间;和2）下丘脑NE的作用是由 他的，AngII和GLU。具体目的是：1）测量NE释放在 哺乳和乳腺神经的大细胞核和BNST 刺激，2）确定中枢His和/或AngII是否影响OT分泌 通过调节泌乳期间NE的释放，以及3）确定神经化学物质 和神经内分泌控制的核内OT释放在ACN/PVN和 儿子这些具体目标将通过不断监测 选定脑区神经化学物质的细胞外浓度 在有意识的、不受限制的哺乳之前、期间和之后， 哺乳期大鼠体内微透析。透析液中的神经化学物质 用放射免疫（OT）和放射酶（NE，His）测定。 此外，药理学激动剂和拮抗剂将用于测试 中枢神经化学物质（NE，OT）和神经调质His，AngII， OLU）对哺乳诱导的外周OT分泌的影响。这些研究将 通过定义以下内容，为IRPG的总体目标做出贡献： 控制中枢NE释放的生理和神经化学因素 催产素和全身性催产素。

This application is a component of an investigator-initiated Interactive Research Project Grant (IRPG) program whose overall objective is to identify and characterize central neurotransmitter systems mediating secretion of oxytocin (OT) in the lactating rat. This component will investigate regulation of norepinephrine (NE) and OT release within hypothalamic nuclei induced by suckling. Previous studies have suggested the importance of intranuclear release of NE and OT in the anterior commissural/paraventricular nucleus area (ACN/PVN), supraoptic nucleus (SON) and the bed nucleus of the stria terminalis (BNST) in systemic OT secretion. However, the stimuli for release and physiological roles of hypothalamic NE and OT in suckling-induced OT secretion are not known. For example, the specific role of somatic stimulation in suckling-induced NE and OT release within hypothalamic nuclei has not been investigated. Furthermore, the importance of intranuclear OT release on systemic OT secretion, and the role of NE in intranuclear OT release are unknown. Finally, the importance of neuromodulators, e.g. histamine (His), angiotensin II (AngII), and glutamate (GLU), which alter CNS NE release, to suckling-induced OT secretion has not been studied. The major objectives of this project are: l) to determine the importance of NE and OT release in the ACN/PVN, SON, and BNST in systemic OT secretion induced by suckling, and 2) to determine if neuromodulators alter intranuclear NE and/or OT secretion evoked by suckling. This project will test the overall hypotheses that l) suckling stimulates NE release in the ACN/PVN, SON and BNST which induces intranuclear OT release and peripheral OT secretion during suckling; and 2) the effects of hypothalamic NE are modulated by His, AngII and GLU. The Specific Aims are: l) measure NE release in the magnocellular nuclei and BNST during suckling and mammary nerve stimulation, 2) determine if central His and/or AngII effect OT secretion by modulating NE release during lactation, and 3) determine neurochemical and neuroendocrine control of intranuclear OT release in the ACN/PVN and SON. These specific aims will be achieved by continuously monitoring extracellular concentrations of neurochemicals in selected brain areas before, during, and following suckling in conscious, unrestrained, lactating rats within vivo microdialysis. Dialysate neurochemicals will be measured with radioimmuno- (OT) and radioenzymatic (NE, His) assays. Furthermore, pharmacological agonists and antagonists will be used to test roles of central neurochemicals (NE, OT) and neuromodulators His, AngII, OLU) on peripheral OT secretion induced by suckling. These studies will contribute to the overall objective of the IRPG by defining the physiological and neurochemical factors that control release of central NE and OT and systemic OT during suckling.