CENTRAL CONTROL OF OXYTOCIN SECRETION

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Oxytocin is a hypothalamic peptide which is important in the reflex initiation of milk ejection and perhaps partuition. Its secretion appears to be centrally controlled by noradrenergic nerves originating in the brain stem and ascending to the hypothalamus. Certain central opiate peptide secreting nerves and a dopaminergic system may also be involved in the control of oxytocin release. The hypothesis can be made that oxytocin secretion is controlled by the ascending noradrenergic tract by mechanisms that resemble descending noradrenergic control of cardiovascular function. In order, to examine the neural mechanisms regulating oxytocin secretion, the ascending adrenergic systems will be pharmacologically ablated (specific aim 1) and certain biochemical hypothalamic events studied either as isolated areas in vitro or using a third ventricular push-pull perfusion system in vivo. A unique aspect of these experiments is that we can monitor both peptidergic and catecholaminergic activity simultaneously. Activity of the oxytocin nerve will be determined by its release into the media in vitro or its presence in the in vivo perfusate. Catecholaminergic activity is concurrently monitored by its in vitro biosynthesis from a labeled precursor, or by the presence of specific amine metabolites in the in vivo perfusate. These are separated and measured using a high performance liquid chromatographic technique. In continuing experiments the hypothalamic location and specificity of adrenergic receptors will be determined in vitro using microdissected hypothalamic areas and a pharmacological approach. Simultaneously the importants of noradrenergic autoreceptors will be examined using the amine biosynthesis/metabolites and in vivo perfusion systems. Finally, the involvement of opiate peptidergic (enkephalinergic) and dopaminergic neurons will be examined using a combination of these approaches. The intent of this proposal is to elucidate the specific neuronal mechanisms responsible for control of oxytocin secretion. It is felt that the studies proposed in this application will yield valuable new information regarding not only the central regulation of this peptide, but also that it might provide a model for the central mechanisms of other neuroendocrine and autonomic events.