The role of arginine vasopressin in the development of tolerance to ethanol in normal and Brattleboro rats.

Administration of AVP and related peptide fragments following ethanol (EtOH) administration has been shown to enhance retention of tolerance to ethanol. The present studies were designed specifically to: (1) examine the influence of AVP given concurrently with EtOH on the development of tolerance to the ataxic and hypothermic effects of EtOH in Long-Evans rats, and (2) to determine if tolerance to these effects develops in Brattleboro rats which are deficient in AVP. In Experiment 1, EtOH (2.5 g/kg, 15% v/v) was administered IP to 2 groups of rats in combination with a SC injection of either AVP (6 micrograms/kg) or an equal volume of saline. Two additional control groups received IP saline injections in combination with either saline or AVP. After 13 days, EtOH-treated rats were significantly more tolerant than saline-treated animals. AVP significantly increased the hypothermic and ataxic effects of EtOH and failed to enhance tolerance development. AVP delayed the extinction of tolerance to the hypothermic (but not the ataxic) effects of ethanol when administered during the extinction phase to rats previously treated with EtOH. In Experiment 2, Brattleboro rats were injected with EtOH or an equivalent volume of saline and tested for ataxia and hypothermia. Rats receiving EtOH failed to demonstrate significant tolerance to either effect of ethanol after 12 treatment days.