Millington, William R.2022-12-212022-12-212016-01-26Başaran, N. F. vd. (2016). "The effect of Gly-Gln [SS-endorphin(30-31)] on morphine-evoked serotonin and GABA efflux in the nucleus accumbens of conscious rats". Neuropeptides, 58, 23-29.0143-41791532-2785https://doi.org/10.1016/j.npep.2016.01.007https://www.sciencedirect.com/science/article/pii/S0143417916000081http://hdl.handle.net/11452/30011Glycyl-L-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide synthesized through the post-translational processing of beta-endorphin(1-31). Central Gly-Gln administration inhibits the rewarding properties of morphine and attenuates morphine tolerance, dependence and withdrawal although it does not interfere with morphine analgesia. In an earlier study, we found that Gly-Gln inhibits morphine-induced dopamine efflux in the nucleus accumbens (NAc), consistent with its ability to inhibit morphine reward. To further investigate the mechanism responsible for its central effects we tested whether i.c.v. Gly-Gln administration influences the rise in extracellular serotonin and GABA concentrations evoked by morphine in the NAc. Conscious rats were treated with Gly-Gln (100 nmol/5 mu l) or saline i.c.v. followed, 2 min later, by morphine (2.5 mg/kg) or saline i.p. and extracellular serotonin and GABA concentrations were analyzed by microdialysis and HPLC. Morphine administration increased extracellular serotonin and GABA concentrations significantly within 20 min, as shown previously. Unexpectedly, Gly-Gln also increased extracellular serotonin concentrations significantly in control animals. Combined treatment with Gly-Gln + morphine also elevated extracellular serotonin concentrations although the magnitude of the response did not differ significantly from the effect of Gly-Gln or morphine, given alone suggesting that Gly-Gin suppressed morphine induced serotonin efflux. Gly-Gln abolished the morphine-induced rise in extracellular GABA concentrations but had no effect on extracellular GABA when given alone to otherwise untreated animals. These data show that Gly-Gln stimulates NAc serotonin efflux and, together with earlier studies, support the hypothesis that Gly-Gln inhibits the rewarding effects of morphine by modulating morphine induced dopamine, GABA and serotonin efflux in the NAc.eninfo:eu-repo/semantics/closedAccessEndocrinology & metabolismNeurosciences & neurologyGlycyl-L-glutamineDipeptideNucleus accumbensMorphineOpioidConditioned place preferenceVentral tegmental areaFreely moving rats5-ht3 receptor antagonistsInduced dopamine effluxCentral-nervous-systemReduces ethanol intakeDorsal raphe nucleusBeta-endorphin5,7-dihydroxytryptamine lesionsAnimalsDipeptidesGamma-aminobutyric acidInjections, intraventricularMaleMorphineNarcoticsNucleus accumbensRatsRats, sprague-dawleySerotoninArticle0003824145000042-s2.0-8498170321523295826861257Endocrinology & metabolismNeurosciencesAging; Amoxicillin; Contractility Invitro4 aminobutyric acidBeta endorphin derivativeDipeptide derivativeDopamineGlycyl levo glutamine[beta endorphin 30-31]MorphineOpiate antagonistSerotoninSodium chlorideUnclassified drug4 aminobutyric acidDipeptideGlycylglutamineMorphineNarcotic agentSerotonin4 aminobutyric acid releaseAmine transportAmino acid transportAnimal experimentAnimal tissueArticleConcentration responseConsciousnessControlled studyDopamine effluxDopamine releaseDose responseDrug efficacyDrug mechanismExtracellular spaceGaba effluxHigh performance liquid chromatographyMaleMicrodialysisNeuromodulationNonhumanNucleus accumbensNucleus accumbens shellPriority journalRatRewardSerotonin effluxSerotonin releaseAnimalDrug effectsIntracerebroventricular drug administrationMetabolismNucleus accumbensSprague dawley rat