Göktalay, GökhanMillington, William R.2021-08-202021-08-202005-11Çavun, S. vd. (2005). "Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal". Journal of Pharmacology and Experimental Therapeutics, 315(2), 949-958.0022-3565https://doi.org/10.1124/jpet.105.091553https://jpet.aspetjournals.org/content/315/2/949http://hdl.handle.net/11452/21482Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide synthesized from beta-endorphin(1-31). Previous investigations have shown that Gly-Gln inhibits the cardiovascular and respiratory depression caused by morphine and beta-endorphin(1-31), but it does not interfere with opioid analgesia. In this study, we tested whether Gly-Gln administration would influence morphine-induced conditioned place preference, tolerance, dependence, or withdrawal. For place preference experiments, rats were conditioned with morphine sulfate (2.5 mg/kg i.p.) or saline on alternate days for 6 days and tested on day 7. Glycyl-glutamine (1-100 nmol i.c.v.) pretreatment inhibited acquisition of a conditioned place preference to morphine significantly. Glycyl-glutamine (100 nmol i.c.v.) also blocked expression of a pre-established morphine place preference, but it did not interfere with acquisition of a conditioned place preference to palatable food, and it did not produce place preference or aversion when given alone to morphine-naive animals. To induce antinociceptive tolerance, rats were treated with morphine (10 mg/kg i.p.) twice daily for 7 days, and morphine antinociception was evaluated with the tail-flick test. Glycylglutamine (100 nmol i.c.v.) pretreatment delayed the onset of morphine tolerance significantly and partially reversed pre-established tolerance. Morphine dependence and withdrawal were assessed by measuring naloxone-precipitated withdrawal symptoms. Glycyl-glutamine inhibited the development of morphine dependence when given to rats twice daily immediately before they received morphine (10 mg/kg i.p.) and suppressed withdrawal symptoms of rats with subcutaneously implanted morphine pellets when administered 5 min before withdrawal was induced with naloxone. Glycyl-glutamine thus attenuates morphine-induced conditioned place preference, tolerance, dependence, and withdrawal without compromising morphine analgesia.eninfo:eu-repo/semantics/closedAccessNaturally-occurring antagonistAcetylcholinesteraseCardiorespiratory depressionPhysical-dependenceRat-brainProopiomelanocortinReceptorsOpioidsBeta-endorphin-(1-27)AntinociceptionPharmacology & pharmacyArticle0002326813000542-s2.0-27144518063949958315216079299Pharmacology & pharmacyAging; Amoxicillin; Contractility Invitro