Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal

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Date

2006-01-13

Journal Title

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Publisher

Elsevier

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.

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Keywords

Pharmacology & pharmacy, Conditioned place preference, Pro-opiomelanocortin, Dipeptide, Beta-endorphin, Nicotine, Opioid, Naloxone, Dependence, Receptor, Smoking, Naltrexone, Cyclic dipeptides, Oligopeptide transporter, Cardiorespiratory depression, Beta-endorphin, Naturally-occurring antagonist

Citation

Göktalay, G. vd. (2006). ''Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal''. European Journal of Pharmacology, 530(1-2), 95-102.