HORMONES AND BRAIN CATECHOLAMINES

激素和大脑儿茶酚胺

• 批准号: 3312713
• 负责人: VICTOR D. RAMIREZ
• 金额: $ 13.4万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3312713
• 关键词: adenylate cyclase; amphetamines; brain metabolism; catecholamines; circadian rhythms; cognition; corpus striatum; cyclic AMP; dopamine; electrochemistry; estrus; high performance liquid chromatography; hormone regulation /control mechanism; neural transmission; neurochemistry; neuroendocrine system; neuropharmacology; progesterone; prolactin; radioassay; sensorimotor system; sex hormones; sympathetic nervous system

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.

该提案旨在澄清和理解的生理性质 激素对大脑多巴胺能神经传递的影响。 黄体酮 (P)、催乳素 (PRL) 和光周期可以显着改变 大鼠黑质纹状体多巴胺（NS-DA）系统的活性。 P 发挥 对该系统的双相作用，先促进后抑制；催乳素 刺激男性而非女性 CS 释放 DA，并且 当局部注入时能够引起梳理和打哈欠行为 雄性大鼠的CS；并且光周期线索似乎发挥了强大的作用 体外CS多巴胺对NS-DA系统的双向影响 上午的活动增加，下午的活动减少 1号和2号大鼠发情间期，这些昼夜变化在发情间期期间被阻止 从发情前期到发情期的过渡。 澄清并更好地理解其作用的生理本质 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。 策略一 - 推拉插管 (PPC) 在线高效液相色谱 电化学检测 (HPLC-EC) 估计同时体内 24小时内一系列神经活性物质的输出 有意识、行为自由的动物的离散大脑区域。 策略二—— 体外灌注来测量时间和幅度 从分离的大脑碎片中释放出神经活性物质 严格可控的实验条件。 策略三—— 生化测定 cAMP 水平和腺苷酸环化酶活性 特定的大脑区域。 使用这三种策略，我们将描绘 生理性质并深入了解 P、PRL 和 光周期影响 NS-DA 神经系统的神经传递。 这些研究的意义在于我们知之甚少 激素对下丘脑外结构 CS 的作用 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 局部输注到完全清醒大鼠的 CS 中，同时 神经化学和行为反应的测量增加了一个新的维度 NS-DA 系统的分析。 我们的研究使用体内和体内 体外方法将有助于更好地了解生物学 荷尔蒙对 CS 的作用并帮助理解荷尔蒙的作用 锥体外系运动功能障碍中的激素。