Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal

• Published in: European journal of pharmacology 2006-01, Vol.530 (1), p.95-102
• Main Authors: Göktalay, Gökhan, Cavun, Sinan, Levendusky, Mark C., Hamilton, Jonathan R., Millington, William R.
• Format: Article
• Language: English
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - pharmacology; Animals; Avoidance Learning - drug effects; Biological and medical sciences; Conditioned place preference; Conditioning (Psychology) - drug effects; Dipeptide; Dipeptides - pharmacology; Dose-Response Relationship, Drug; Injections, Intraventricular; Injections, Subcutaneous; Male; Mecamylamine - pharmacology; Medical sciences; Nicotine; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Nicotinic Antagonists - pharmacology; Opioid; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Pro-opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa - agonists; Substance Withdrawal Syndrome - prevention & control; Time Factors; β-endorphin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.11.034

Glycyl-glutamine (Gly-Gln) is an inhibitory dipeptide synthesized from β-endorphin 1–31. 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.