© 2017 IBRO The mode of action of L-DOPA on excitatory synaptic transmission in second-order neurons of the nucleus tractus solitarius (NTS) was studied using the rat brainstem slices. Superfusion of L-DOPA (10 μM) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without any effect on the amplitude. A low concentration (1 μM) was ineffective on the mEPSCs, and the highest concentration (100 μM) exerted a stronger inhibitory effect. L-DOPA (10 μM) decreased the amplitude of EPSCs (eEPSCs) evoked by electrical stimulation of the tractus solitarius and increased the paired-pulse ratio. The inhibitory effects of L-DOPA on mEPSCs and eEPSCs were similar to those of dopamine (100 μM). The effects of L-DOPA were blocked by a competitive antagonist, L-DOPA methyl ester (100 μM) and also by a D2 receptor antagonist, sulpiride (10 μM), while those of dopamine were blocked by the latter but not by the former. In reserpine (5 mg/kg, s.c.)-treated rats, the effects of L-DOPA on both mEPSCs and eEPSCs were completely abolished, but those of dopamine remained unchanged. The present results suggest a possibility that L-DOPA may induce the release of dopamine from the axon terminals in the NTS and the released dopamine suppresses the glutamatergic transmission through activation of the presynaptic D2 receptors.