GLYCYL-L-GLUTAMINE INJECTED CENTRALLY SUPPRESSES ALCOHOL-DRINKING IN P-RATS

Recent reports show that central beta-endorphin (1-31) injection augme nts the volitional intake of alcohol. Correspondingly, alcohol drinkin g stimulates beta-endorphin (1-31) release from the hypothalamus of th e rat. Glycyl-l-glutamine (Gly-Gln) is produced in beta-endorphin-cont aining neurons and is coreleased with beta-endorphin(1-31) and other p rocessing products. Because Gly-Gln is apparently an endogenous antago nist of beta-endorphin(1-31) in several systems, the present study was designed to investigate the hypothesis that Gly-Gln injected ICV woul d alter voluntary alcohol drinking in the genetic, high-alcohol-prefer ring P rat. After a guide tube was implanted stereotaxically above the lateral cerebral ventricle, the rats were offered 3-30% alcohol over 10 days, and then given their maximally preferred concentration of alc ohol in the presence of water for the remainder of the experiment. Gly -Gln or artificial cerebrospinal fluid (CSF) vehicle then was injected ICV in a dose of 10 or 100 nmol for 3 consecutive days, which was fol lowed by a 7-day postinjection interval. Gly-Gln suppressed significan tly the intakes of alcohol in terms of both g/kg and proportion to tot al fluid. During the postinjection days, alcohol drinking continued to be suppressed, whereas neither the daily intakes of food or water nor the body weights of the rats were changed. The present results are co nsistent with the concept of a functional antagonism by Gly-Gln of the role of beta-endorphin(1-31) in mediating certain central functions. These results demonstrate that alcohol consumption is suppressed by th e direct intracerebral application of this unique peptide. (C) 1998 El sevier Science Inc.