NEUROCHEMICAL CONTROL OF OXYTOCIN RELEASE

哺乳引发神经内分泌反射，释放催产素(OT) 从视上区和室旁区神经元的轴突终末发出 核(SON/PVN)进入大循环。然而，人们对此知之甚少 到目前为止，关于涉及的神经化学机制。该计划的目的是 拟议的研究是为了阐明促进和抑制 哺乳反应中控制OT分泌的神经化学机制 在大鼠中，重点是儿茶酚胺和阿片类药物的作用 中枢神经水平和神经叶水平的多肽 (NL)。将依赖于对OT浓度的直接分析 血浆使用放射免疫分析，而不是乳房内压或牛奶喷射， 这些指标是OT释放的间接指标。两个特定的相互关联的 假说将被检验：1)哺乳激活中枢去甲肾上腺素能 通过SON/PVN和/或其他系统中的操作来调节OT释放的系统 影响这些神经分泌中心的下丘脑区域。2) 下丘脑对哺乳反应释放催产素受多巴胺的调节 (DA)由结节-垂体轴突释出，b)由内源性阿片类药物释放 可作为OT的递质的神经肽，以及c)通过 交感肾上腺循环中的去甲肾上腺素和肾上腺素 起源。(肾上腺素从交感-肾上腺系统释放到 对哺乳作出反应的大鼠的循环。我们会调查的 这些假说是通过确定a)哺乳是否影响 多巴胺、去甲肾上腺素和5-羟色胺(5H-T)在大脑和大脑不连续区域的周转 在NL中；b)大脑单胺类物质的局部耗竭是否由 神经毒素，6-羟基多巴胺(NE和DA)和5，7-二羟色胺 (对于5H-T)，影响哺乳诱导的OT的释放；c) 中枢和外周活性单胺激动剂和拮抗剂以及 肾上腺切除对哺乳期催产素释放的影响；d)阿片类药物的影响 阿片类神经肽的激动剂和拮抗剂对OT释放的影响 吸奶；以及e)鸦片类药物是否影响大脑和中脑皮层的变化 哺乳引起的儿茶酚胺代谢。我们还将在体外使用 方法(分离的NL和NL突触小体)分析 单胺类和阿片类激动剂和拮抗剂对催产素分泌的影响 直接在民族解放阵线。

Suckling initiates a neuroendocrine reflex which releases oxytocin (OT) from the axon terminals of neurons in the supraoptic and paraventricular nuclei (SON/PVN) into the general circulation. Little, however, is known to date about the neurochemical mechanisms involved. The purpose of the proposed investigation is to elucidate the facilitatory and inhibitory neurochemical mechanisms controlling OT secretion in response to suckling in the rat, with emphasis on the roles of catecholamines and opioid peptides both at the level of the CNS and at the level of the neural lobe (NL). Reliance will be placed upon direct analysis of OT concentrations in the plasma using RIA rather than intramammary pressure or milk ejection, which are indirect indices of OT release. Two specific interrelated hypotheses will be tested: 1) Suckling activates central noradrenergic systems that regulate OT release via actions in the SON/PVN and/or in other hypothalamic areas that influence these neurosecretory centers. 2) The release of OT in response to suckling is modulated in the NL a) by dopamine (DA) released from tuberohypophysial axons, b) by endogenous opioid neuropeptides which may serve as transmitters with OT, and c) by circulating norepinephrine (NE) and epinephrine (E) of sympathetic adrenal origin. (Epinephrine is released from the sympathetic-adrenal system into the circulation of the rat in response to suckling.) We will investigate these hypotheses in vivo by determining a) whether suckling affects the turnover of DA, NE, and serotonin (5H-T) in discrete areas of the brain and in the NL; b) whether localized depletions of brain monoamines by the neurotoxins, 6 hydroxydopamine (for NE and DA) and 5, 7 dihydroxytryptamine (for 5H-T), affect the suckling-induced release of OT; c) the effects of centrally and peripherally active monoamine agonists and antagonists and of adrenalectomy upon OT release during suckling; d) the effects of opiate agonists and antagonists and of opioid neuropeptides upon OT release during suckling; and e) whether opiates influence the changes in brain and NL catecholamine turnover induced by suckling. We will also employ in vitro methods (isolated NL and NL synaptosomes) to analyze the effects of monoaminergic and opiate agonists and antagonists upon OT secretion directly at the NL.