Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal

Goktalay G., Cavun S., Levendusky M., Hamilton J., Millington W.

European Journal of Pharmacology, cilt.530, sa.1-2, ss.95-102, 2006 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 530 Sayı: 1-2
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1016/j.ejphar.2005.11.034
  • Dergi Adı: European Journal of Pharmacology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.95-102
  • Anahtar Kelimeler: 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 Uludağ Üniversitesi Adresli: Evet

Özet

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.