title: Glycyl-glutamine in nucleus accumbens reduces ethanol intake in alcohol preferring (P) rats.
abstract: Opioid peptides and glycyl-glutamine (Gly-Gln) have been implicated in the control of ethanol consumption. A recognized beta-endorphin cleavage product, Gly-Gln, inhibits voluntary alcohol consumption when microinjected into the nucleus accumbens (AcbSh) of P rats. To evaluate the site-specific efficacy of Gly-Gln on ethanol consumption following AcbSh application, ethanol preferring (P) rats were allowed to establish individual baseline ethanol/water consumption utilizing a voluntary self-administration paradigm. Subsequent to baseline ethanol consumption being established, bilateral guide cannulae were stereotaxically implanted +1 mm dorsal to the AcbSh for subsequent Gly-Gln (100 nmol/microl) or saline vehicle (1 microl) injections. Alcohol intake, body weight, and water intake were measured at 24 h post-injection intervals. Unilateral Gly-Gln injections reduced ethanol consumption 35.6% (P < 0.05) from pre-established baseline consumption (6.24 +/- 0.64 g/kg to 4.06 +/- 0.28 g/kg). Bilateral Gly-Gln injections further reduced consumption to 51.9% (6.4 +/- 1.0 g/kg to 3.08 +/- 0.65 g/kg at 24 h (P < 0.01) below established baseline values within 24 h without significant changes in body weight or water consumption. Also, the amino acid constituents of the dipeptide had no influence on ethanol consumption behavior; however, Gly-Gln efficacy was shown to be comparable to central beta-endorphin-(1-27) or intraperitoneal (i.p.) naltrexone-induced suppression of ethanol intake. These data indicate that the AcbSh exhibits a site-specific sensitivity to the suppressive actions of Gly-Gln or beta-endorphin-(1-27) injections that modulate voluntary ethanol consumption in P rats. These findings support the broader concept that select forebrain opioid-responsive neural sites may influence the development or expression of alcohol abuse syndromes in animal models or humans.
authors.affiliation: Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA. reschg@umkc.edu
authors.forename: Garth E
authors.initials: GE
authors.lastname: Resch
authors.forename: Shyam
authors.initials: S
authors.lastname: Shridharani
authors.forename: William R
authors.initials: WR
authors.lastname: Millington
authors.forename: David R
authors.initials: DR
authors.lastname: Garris
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Simpson
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000437:Alcoholism / Q000188:drug therapy; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism; D001615:beta-Endorphin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002492:Central Nervous System Depressants; D004151:Dipeptides; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C039788:glycylglutamine; D000431:Ethanol; D001615:beta-Endorphin