This research proposal is designed to study the electrophysiological effects of ethanol on hypothalamic neural circuits related to ethanol- induced sexual dysfunction, hypothermia, and inhibition on vasopressin release. In addition, this proposal also attempts to uncover the neural mechanism responsible for the development of functional tolerance to and physical dependence on some of these ethanol induced effects. For the attainment of the objective, the electrophysiological approach of extracellular recording at the single nerve cell level, antidromic identification, microiontophoresis, and micro-pressure ejection of tested agents will be used. Experimental rats will be pharmacologically manipulated with ethanol to produce a given physiological state (sexual dysfunction, hypothermia, or inhibition of vasopressin release) or to possess tolerance to and physical dependence on ethanol. In these animals, extracellular action potentials of hypothalamus (for the expression of sexual function), (2) the preoptic and anterior hypothalamic areas (for body temperature regulation), and (3) supraoptic and paraventricular nuclei (for the release of vasopressin). The neuronal characteristics of hypothalamic neurons (recorded in each brain region) corresponding to a given physiological state will be identified with respect to firing rate, firing pattern, and pharmacological responsiveness to micro-applied agents. Neuronal characteristics from various physiological states will be compared for uncovering the neuronal mechanism responsible for the impairment of hypothalamic functions by ethanol, and for the development of tolerance to and physical dependence on ethanol. It is anticipated that this study will help to understand the neuronal adaptive changes imposed on hypothalamic neurons by ethanol upon chronic administration. In addition, data to be obtained from studies dealing with vasopressinergic neurons might provide important insight into how ethanol might alter the extrahypothalamic vasopressinergic neurons leading to the retention of tolerance. Finally, it is hoped that results of this research will provide important information related to the treatment of medial complications resulting from alcohol abuse, tolerance, and physical dependence.
