The aim of the proposed studies is to examine the influence of neurohypophyseal hormones and related peptides on the development and maintenance of CNS tolerance to ethanol. Previous work has implicated noradrenergic systems as necessary for development of ethanol tolerance, and the neurohypophyseal peptides have been reported to affect the metabolism of norepinephrine in brain. An animal model for chronic consumption of ethanol will be used in which the development and expression of tolerance and physical dependence can be monitored by behavioral and physiological means, and in which the effects of the peptides on these phenomena, both during normal and altered catecholaminergic function, can be assessed. In this context, ethanol tolerance may be considered as a model for CNS adaptive phenomena, some of which (i.e. learning or memory) are also influenced via centrally-mediated effects of neurohypophyseal peptides.