Structural requirements for neurohypophyseal peptide maintenance of ethanol tolerance

Tolerance to the hypnotic effect of ethanol in mice is prolonged by daily subcutaneous administration of arginine vasopressin and certain analogs of this hormone. The major structural requirement for maintenance of ethanol tolerance by these peptides appears to be the N-terminal "ring" structure of vasopressin containing two amino acid residues with aromatic side chains. Peptides structurally related to the C-terminal portion of the neurohypophyseal hormones are less active in maintaining tolerance than the intact hormones. The structure-activity pattern observed for the effects of peptides on ethanol tolerance is similar to that described for neurohypophyseal peptide inhibition of extinction of an active avoidance response, an action thought to reflect peptide effects on memory consolidation. The results are in line with our hypothesis that similar CNS recognition sites may mediate neurohypophyseal peptide effects on ethanol tolerance and certain memory processes. The neurohypophyseal hormones and analogs did not affect the hypnotic or hypothermic response to an acute injection of ethanol, indicating that the determination of tolerance was not influenced by a direct peptide-ethanol interaction. The hormones themselves, however, did cause a drop in body temperature in the mice, which could be a result of either central or peripheral hormonal actions.