Cyclo-glycyl-glutamine inhibits ethanol intake in P and Sprague–Dawley rats

Abstract

Peptide inhibitors of ethanol consumption have shown promise. The purpose of this study was to test the cyclized form of the opioid-derived dipeptide, glycyl-L-glutamine to reduce ethanol consumption after either peripheral injections or site-specific injections into the nucleus accumbens (NAC) of high drinking and low drinking rats. Following I.P. cyclo-glycyl-glutamine (c-GQ), the data show a mean decrease in ethanol intake of 34.4% in P rats, and 39.4% in Sprague-Dawley rats at doses between 5 and 25mg/kg. The data show that peripherally administered c-GQ is effective in reducing ethanol consumption in both high (P) and low (SD) drinking strains of rats and suggests a therapeutic potential.

A liquid chromatography–tandem mass spectrometry assay for detection and quantitation of the dipeptide Gly-Gln in rat brain

“…Gly-Gln is a known inhibitor of voluntary ethanol drinking in rats acting within the nucleus accumbens, and has also been shown to inhibit the reward benefiting effects of morphine and nicotine [3; 4; 5; 6; 7; 8; 9]. An assay for Gly-Gln would be of great utility for further investigation of this effect and in efforts to exploit this effect for the development of novel anti-addictive agents.…”

“…Two cleavage products of β-endorphin 1-31 – β-endorphin1-27 and Gly-Gln (β-endorphin 30-31) – are implicated in reduction of ethanol intake [1; 2; 3; 4; 5; 6]. β-endorphin1-27 and Gly-Gln act in different ways.…”