Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal
European Journal of Pharmacology, vol.530, no.1-2, pp.95-102, 2006 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 530 Issue: 1-2
- Publication Date: 2006
- Doi Number: 10.1016/j.ejphar.2005.11.034
- Journal Name: European Journal of Pharmacology
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.95-102
- Keywords: opioid, nicotine, beta-endorphin, dipeptide, pro-opiomelanocortin, conditioned place preference, NATURALLY-OCCURRING ANTAGONIST, BETA-ENDORPHIN, CARDIORESPIRATORY DEPRESSION, OLIGOPEPTIDE TRANSPORTER, CYCLIC DIPEPTIDES, NALTREXONE, SMOKING, RECEPTOR, DEPENDENCE, NALOXONE
- Bursa Uludag University Affiliated: Yes
Abstract
Glycyl-glutamine (Gly-Gln) is an inhibitory dipeptide synthesized from β-endorphin1-31. Previously, we showed that Gly-Gln inhibits morphine conditioned place preference, tolerance, dependence and withdrawal. In this study, we tested whether Gly-Gln's inhibitory activity extends to other rewarding drugs, specifically nicotine. Rats were conditioned with nicotine (0.6 mg/kg, s.c.) for four days and tested on day five. Glycyl-glutamine (100 nmol i.c.v.) inhibited acquisition and expression of a nicotine place preference significantly. Cyclo(Gly-Gln) (100 nmol i.c.v. or 25 mg/kg i.p.), a cyclic Gly-Gln derivative, blocked expression of nicotine place preference but Gly-d-Gln (100 nmol i.c.v.) was ineffective. To study nicotine withdrawal, rats were treated with nicotine (9 mg/kg/day) for seven days and conditioned place aversion was induced with mecamylamine (1 mg/kg, s.c.). Glycyl-glutamine blocked acquisition of place aversion to mecamylamine but not U50,488, a kappa opioid receptor agonist. Glycyl-glutamine thus inhibits the rewarding effects of nicotine and attenuates withdrawal in nicotine dependent rats. © 2005 Elsevier B.V. All rights reserved.