OPIOID CONTROL OF THE NEUROENDOCRINE SUPRAOPTIC NUCLEUS

加压素和催产素在维持血浆中起着至关重要的作用。 哺乳动物的体积和渗透压以及各种生殖功能。 这些激素是由巨细胞神经内分泌细胞分泌的 下丘脑-神经-垂体系统。有明确的证据表明 内源性阿片类药物通过直接抑制电活动和分泌活动 对这些神经元的作用，但作用机制和选择性 催产素能神经元或加压素能神经元尚不清楚。阿片类药物 影响表现出容忍和依赖，并且在生理上是相关的 由于应用阿片类拮抗剂纳洛酮也可能影响激素 分泌物表明有紧张性阿片类药物输入。外源基因的作用 这些神经内分泌细胞上的阿片类药物表现出耐受性和依赖性，a 明确的迹象表明这些神经元的正常功能在 人类在药物滥用或治疗情况下长期使用阿片类药物。 在这里提出的研究的目的是调查 阿片类药物对细胞膜上特定离子电导的影响 催产素能和加压素能神经元的轴突终末。 为了实现这些目标，全电池电压钳位技术将 用于研究神经元上阿片受体的性质， 受体激活对不同电压门控性高血压大鼠的影响 电压不敏感离子电流和受体-离子通道的性质 耦合。在当前夹具下进行的录制将允许总体 阿片类药物对膜电位和放电活动的影响 检查过了。记录将从分离的神经内分泌细胞进行 成人视上核和孤立轴突终末的分布 从神经垂体中分离出来。此方法允许对 细胞体水平的兴奋性及其对细胞的影响 在轴突水平上研究兴奋-分泌耦合 终点站。 这些研究将提供有关阿片类药物的重要新信息。 这个神经内分泌系统中的机制被认为是一个模型 所有哺乳动物的神经内分泌细胞。此外，这些研究将是 独特之处在于将研究神经递质的影响 在单个神经元系统的水平上的电生理学 细胞体和轴突终末。

Vasopressin and oxytocin have crucial roles in the maintenance of plasma volume and osmolality and in various reproductive functions in mammals. These hormones are secreted by the magnocellular neuroendocrine cells of the hypothalamo-neurohypophysial system. There is clear evidence that endogenous opioids inhibit the electrical and secretory activity by direct actions on these neurons but the mechanisms of action and selectivity for oxytocinergic or vasopressinergic neurons are not clear. The opioid effects show tolerance and dependence, and are physiologically relevant since application of the opioid antagonist naloxone may also affect hormone secretion indicating a tonic opioid input. The effects of exogenous opioids on these neuroendocrine cells show tolerance and dependence, a clear indication that the normal function of these neurons is impaired in humans chronically using opioids in drug abuse or therapeutic situations. The goal of the research proposed here is to investigate the effects of opioids on specific ionic conductances in the membrane of the cell body and the axon terminals of oxytocinergic and vasopressinergic neurons. To achieve these objectives, whole-cell voltage clamp techniques will be used to investigate the nature of opioid receptors on the neurons, the effect of receptor activation on various voltage-gated and voltage-insensitive ionic currents, and the nature of receptor-ion channel coupling. Recordings made under current clamp will permit the overall effects of opioids on membrane potential and firing activity to be examined. Recordings will be made from dissociated neuroendocrine cells of the adult supraoptic nucleus and from isolated axon terminals dissociated from the neurohypophysis. This approach permits effects on excitability at the level of the cell body and effects on excitation-secretion coupling to be studied at the level of the axon terminal. These studies will provide important novel information on opioid mechanisms within this neuroendocrine system which is considered as a model for all mammalian neuroendocrine cells. Further, the studies will be unique in that neurotransmitter effects will be studied electrophysiologically within a single neuronal system at the level of the cell body and the axon terminal.