title: Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal.
abstract: Glycyl-glutamine (Gly-Gln) is an inhibitory dipeptide synthesized from beta-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.
authors.affiliation: Department of Basic and Pharmaceutical Sciences, Albany College of Pharmacy, Union University, NY 12208, USA.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Göktalay
authors.forename: Sinan
authors.initials: S
authors.lastname: Cavun
authors.forename: Mark C
authors.initials: MC
authors.lastname: Levendusky
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Hamilton
authors.forename: William R
authors.initials: WR
authors.lastname: Millington
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control; D013997:Time Factors
chemical_list: D004151:Dipeptides; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010456:Peptides, Cyclic; D017473:Receptors, Opioid, kappa; C039788:glycylglutamine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D008464:Mecamylamine; D009538:Nicotine