HORMONES AND BRAIN CATECHOLAMINES

这项建议旨在澄清和了解心力衰竭的生理本质 激素对脑多巴胺能神经传递的影响。 孕酮(P)、催乳素(PRL)和光周期均能显著改变 大鼠黑质纹状体多巴胺(NS-DA)系统的活性。P施加了一个 对这一系统的双相作用，先促进后抑制；催乳素 刺激雄性CS和IS释放DA，但不刺激雌性CS和IS 能够唤起梳理和打哈欠的行为，当注入局部 雄性大鼠的CS；而光周期信号似乎发挥着强大的作用 体外CS多巴胺对NS-DA系统的双向影响 活动在上午增加，下午减少。 间情期1和2的大鼠，这些昼夜变化在 从发情前期到发情期的过渡。 为了澄清和更好地了解影响的生理性质 光周期、激素及其相互作用对NS-DA功能的影响 系统我们选择了三种策略。策略I--推拉式插管 (PPC)与高效液相色谱联用 电化学检测(高效液相色谱-电化学法)评价体内的同步 一系列神经活性物质在24小时内的输出 有意识的、行为自由的动物的离散大脑区域。战略II-- 在体外灌流以测量时间和大小 从分离的脑碎片中释放出的神经活性物质 严格可控的实验条件。战略III-- 大鼠cAMP水平和腺苷环化酶活力的生化测定 特定的大脑区域。使用这三种策略，我们将描绘出 生理本质，并深入了解P、PRL和 光周期影响NS-DA神经元系统的神经传递。 这些研究的意义在于人们对此知之甚少 激素对下丘脑外结构CS的作用 它将神经内分泌机制与运动、感觉和认知联系起来 NS-DA系统的功能。激素与药物的结合 同时向完全清醒大鼠的CS局部注入 神经化学和行为反应的测量增加了一个新的维度 对NS-DA系统的分析。我们的研究使用了体内和体内 体外方法学将有助于更好地洞察肿瘤的生物学 荷尔蒙对CS的作用并有助于理解 锥体外系运动功能障碍中的激素。

This proposal aims to clarify and understand the physiological nature of the effects of hormones on brain dopaminergic neurotransmission. Progesterone (P), prolactin (PRL) and photoperiod can markedly modify the activity of the rat nigrostriatal dopamine (NS-DA) system. P exerts a biphasic action on this system, facilitation followed by inhibition; PRL stimulates the release of DA from male but not from female CS and is capable to evoke grooming and yawning behavior when infused locally within the CS of male rats; and photoperiodic cues appear to exert robust bidirectional influences on the NS-DA system since in vitro CS dopamine activity increases in the morning and decreases in the afternoon in diestrus 1 and 2 rats and these diurnal variations are blocked during the transition from proestrus-estrus. To clarify and better understand the physiological nature of the effect of photoperiod, hormones and their interactions upon the function of the NS-DA system we have chosen three strategies. Strategy I - Push-Pull Cannula (PPC) on-line with High Performance Liquid Chromatography with Electrochemical Detection (HPLC-EC) to estimate the simultaneous in vivo output of a series of neuroactive substances during a 24h period from discrete brain areas of conscious, freely behaving animals. Strategy II - in vitro superfusion to measure the temporal and magnitude of the neuroactive substances released from isolated brain fragments under rigorously controllable experimental conditions. Strategy III - biochemical determinations of cAMP levels and adenylate cyclase activity in specific brain areas. Using these three strategies we will delineate the physiological nature and gain an insight in mechanisms by which P, PRL and photoperiod affect neurotransmission of the NS-DA neuronal system. The significance of these studies reside in the fact that little is known of the action of hormones upon the CS, an extra-hypothalamic structure which bridges neuroendocrine mechanisms with motor, sensory and cognitive functions of the NS-DA system. The combination of hormone and drug infusions locally into the CS of fully awake rats with simultaneous measurements of neurochemical and behavioral responses add a new dimension to the analyses of the NS-DA system. Our studies using in vivo and in vitro methodologies will help to gain a better insight on the biology of hormonal action upon the CS and to aid the understanding of the role of hormones in extrapyramidal motor disfunctions.