Objective Recent studies showed that the oxytocin (OT),a neurohypophyseal neuropeptide which affected adaptive central nervous system processes related to drug addiction,blocked glutamate activation.The present study was designed to investigate the effects of OT and atosiban (Ato),a selective inhibitor of OT,on extracellular glutamate (Glu) release induced by methamphetamine (MAP) in the medial prefrontal cortex (mPFC) of mice.Methods The level of Glu was determined by microdialysis coupled to high performance liquid chromatography and fluorescence detection.Results OT (2.5 μg/mouse,i.c.v.) attenuated the Glu release induced by MAP (2.0 mg/kg,i.p.) in mPFC at the dose that did not modify the basal release of Glu.This effect could be antagonized by Ato at a dose of 10.0 μg/mouse,which did not affect the basal release of Glu.Conclusion This study gives the first evidence that oxytocin receptor is involved in the inhibition of OT on MAP-induced Glu release in mouse mPFC.