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Cyclo (His-Pro) or CHP is a cyclic dipeptide endogenous to the central nervous system of a variety of animal species including humans. Administration of exogenous CHP to animals has been shown to elicit a variety of biologic activities. In eliciting some of its many biologic activities, CHP acts to facilitate dopaminergic neurotransmission. The endogenous brain level of CHP is much higher in mice with hereditary low alcohol preference (DBA/2J) than in those with high alcohol preference (C57BL/6J). Furthermore, oral administration of exogenous CHP to alcohol preferring C57BL/6J mice results in a significant disease in voluntary alcohol consumption. In light of these data it is out long-term goal to develop CHP as an agent to treat alcohol abuse in humans. Therefore, we have set out two specific aims in Phase I of the SBIR: 1)to examine the effect of route of administration and dosage of CHP on serum levels of CHP in normal Sprague-Dawley rats, and 2)to compare oral and subcutaneous routes of CHP administration for their efficacy to decrease alcohol intake. The efficacy of CHP in reducing voluntary alcohol consumption will be evaluated using a physiologic model (voluntary alcohol drinking) and two genetic models (alcohol preferring P and high ethanol preferring HEP rats) of alcohol abuse. PROPOSED COMMERCIAL APPLICATION: Treatment of alcoholism with a naturally occurring substance for voluntary use for non-compliant persons.