Centrally acting peptides and tolerance to ethanol.

Abstract

Among the many factors that may influence the development or expression of functional tolerance to or physical dependence on ethanol is the neurohypophyseal hormone, arginine vasopressin (AVP). This peptide hormone, administered exogenously, maintains ethanol tolerance in animals once such tolerance has been established. An analog of the hormone has also been reported to facilitate the development of ethanol tolerance and to exacerbate ethanol withdrawal symptomatology. Neurohypophyseal hormones and structurally related peptides have previously been shown to influence learning or memory; however, structure-activity analyses reveal differences in the structural requirements for maintenance of ethanol tolerance as compared to facilitation of memory processes. Therefore, these phenomena may represent CNS adaptive processes which are subserved by different mechanisms, or are differentially sensitive to particular peptides. The initial sensitivity of an animal to ethanol can also be affected by peptides, notably thyrotropin releasing hormone (thyroliberin, TRH). TRH antagonizes many of the initial responses to ethanol, perhaps by non-specific means. AVP, however, appears to potentiate the sedative effect of an acute dose of ethanol. Neurohypophyseal peptides also modulate ethanol intake. Thus, these neuropeptides, which have been localized to many areas of brain, may serve as endogenous modulators of various parameters related to ethanol consumption.