Ethanol Tolerance in the Rat Neurohypophysis: a Dissertation

One of the main components underlying drug addiction is the emergence of tolerance. Although its development is a complex issue, and is believed to have both psychological and physiological connotations , it is clear that some physiological change must occur that would enable an organism to withstand drg concentrations lethal to a naive system. The purpose of this thesis was to identify and study a physiological mechanism, whose characteristics were altered due to chronic exposure to ethanol. Vasopressin (A VP), whose primary function is to control water balance , release from the neurohypophysis is suppressed by an acute etl;anol challenge. Therefore, I hypothesized; 1) that chronic ethanol exposure would reduce the normal suppression of A VP release during an acute ethanol challenge and 2) that the ion channels that are acutely sensitive to ethanol, involved in the control of A VP release , would exhibit a change in their ethanol sensitivity and characteristics. To study the hypothesis , I utilized the neurohypophysis from rats chronically exposed to ethanol and yoked controls to determine whether chronic exposure would modify the acute ethanol sensitivity of the neurohypophysial vasopressin release mechanism. I examined whether the long-term ethanol exposure affected the suppression of vasopressin release from either or both the intact neurohypophysis and the isolated neurohypophysial terminals. In addition, I investigated how chronic exposure affected two types of potassium channels , the ethanol sensitive large conductance Ca +2 -activated (BK) channel