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Objective Methylphenidate (MPH),a reuptake inhibitor of dopamine (DA) and norepinephrine (NE),is widely used as a therapeutic drug for the attention deficit hyperactivity disorder (ADHD).However,the role of MPH in regulating excitatory synaptic transmission on the prefrontal cortex (PFC) neurons is poorly understood.Methods In the present study,we examined the effect of MPH on excitatory synaptic transmission in layer IV/V pyramidal cells of rat medial prefrontal cortex (mPFC) by using whole-cell patch-clamp recording.Results Bath application of MPH (50 μmol/L) produced a significant enhancement in the evoked excitatory postsynaptic currents (eEPSCs) mediated by ionotropic glutamate receptors in layer Ⅳ/Ⅴ pyramidal cells of the mPFC.In addition,MPH (50 μmol/L) significandy enhanced both NMDA-receptor and non-NMDA-receptor mediated eEPSC.In the catecholamine-depleted slices,MPH (50 μmol/L) significantly enhanced NMDA-receptor mediated eEPSC,but produced no effect on non-NMDA-receptor mediated eEPSC.