DESCRIPTION: Applicant's Abstract Opioids interact with receptors on neurons, leading to a variety of effects, e.g., analgesia, euphoria, and diuresis. It is not known, however, whether the primary target for these effects are at somata and/or synapses in the central nervous system. The electrical and secretory activities of the hypothalamo-neurohypophysial system are affected by both exogenous and endogenous opioids. The specific effects of opioids on membrane ionic conductances in these neurons and their nerve terminals, however, are unknown. Vasopressin and oxytocin have crucial roles in fluid homeostatic mechanisms and in various reproductive functions. These peptide neurohormones are synthesized by magnocellular neurons of the hypothalamus and secreted from neurohypophysial terminals. Furthermore, the hypothalamo-neurohypophysial system develops tolerance and dependence to morphine during chronic administration suggesting that this central nervous system is a good model for studying the physiological mechanisms underlying these phenomena. The hypothalamo-neurohypophysial system affords the unique opportunity of unraveling the complicated effects of opioids in the central nervous system by comparing such effects on the different components of central nervous system neurons. The goal of the research proposed here is to determine membrane mechanisms that mediate opioid-induced modifications of neurohormone secretion and the responses of nerve terminals vs. neuronal cell bodies. To achieve these objectives, perforated patch recordings of action potentials and of Ca2+ and K+ currents will be made from identified, isolated neuroendocrine cells and nerve terminals obtained from the hypothalamo-neurohypophysial system of adult rats. Effects on release will be compared between magnocellular neurons and NH terminals by the use of radioimmununoassays and capacitance measurements. These studies will provide a unique opportunity to determine how acute opioid effects occur at the somata and or terminals of central nervous system neurons.