Arginine vasopressin (AVP), a mammalian antidiuretic hormone, and related peptides, when administered exogenously, prolong the duration of tolerance to ethanol. The similarities between neurohypophyseal peptide effects on tolerance and previously reported effects on memory consolidation supported the hypothesis that, as examples of CNS adaptation, these phenomena may share underlying mechanisms. We found that intracerebroventricular (i.c.v.) injections of AVP and related peptides maintained tolerance in mice, suggesting that the peptides act centrally to modulate neuronal systems influencing tolerance. We have also obtained evidence, in mice and rats, that a specific peptide antagonist, administered i.c.v., can enhance the rate of dissipation of functional tolerance to ethanol. These findings suggest that endogenous AVP may be involved in the maintenance of ethanol tolerance. The effects of AVP on environment-dependent ethanol tolerance have also been studied. This type of tolerance arises as a conditioned compensatory response of the animal to the effects of ethanol, and is more pronounced in an environment in which the animal has previously been exposed to ethanol. Thus, environment-dependent tolerance is thought to have a prominent """"""""learned"""""""" component; AVP maintained this tolerance, which was produced by daily injections of ethanol. However, AVP inhibited the acquisition of environment-dependent tolerance, possibly by interfering with the animals' perception of the cues associated with ethanol administration. Preliminary studies of the biochemical effects of AVP in the brain have also been performed. Understanding the role of the peptide hormones in development, expression, and dissipation of various forms of tolerance to ethanol may lead to benign means for the manipulation of tolerance development and, possibly, of ethanol intake.
