Role of endogenous Cyclo(His-Pro) in voluntary alcohol consumption by alcohol-preferring C57BL mice

PRASAD, C. Role of Endogenous Cyclo(His-Pro) in Voluntary Alcohol Consumption by C57BL Mice. PEPTIDES-Cyclo (His-Pro) or CHP is a cyclic dipeptide endogenous to the brain of a variety of animal species including man. Administration of exogenous peptide to rodents has been shown to exhibit a variety of biological activities some of which appear to be mediated via a dopaminergic mechanism. Since a hypodopaminergic state has been associated with excessive drinking in animal models as well as man, we have explored the potential role of CHP in alcohol-preferring C57BL mice, The results of this study show that the level of CHP, a peptide that mimics dopamine in many of its pharmacologic actions, is lower in brains of alcohol-preferring C57BL mice compared to alcohol non-preferring DBA2 mice. Furthermore, administration of exogenous CHP to C57BL mice caused a pronounced decrease in their voluntary alcohol consumption. In conclusion, endogenous CHP may play a role in risk for developing excessive alcohol use by modulating central dopaminergic tone. (C) 2001 Elsevier Science Inc. All rights reserved.