To our knowledge, it is the first study directly comparing the effects of DA on AMPA/KA and NMDA receptors-mediated components of the ECSCs showing that DA exerted a stronger inhibition of NMDA than AMPA/KA receptor-mediated EPSCs. The latter finding supports the idea that there is direct D1-NMDA receptors interaction at cellular level. In addition, a recent study suggests a dopamine triggered heterosynaptic plasticity mechanism, likely mediated presynaptically located D1 recetors and expressed by presynaptic inhibition of GABA release. Most studies that have examined the effects of DA on glutamatergic neurotransmission in the nAcb have found a D1like receptors-mediated depression of excitatory responses in agreement with our results. In vitro experiments have shown that this inhibition was mediated by presynaptic dopaminergic receptors located on glutamatergic terminals and are consistent with the demonstration that DA inhibited glutamate release in nAcb. DA receptors are distributed on both presynaptic glutamatergic terminals and postsynaptic membrane of MS neurons in the nAcb. Therefore, DA may have exerted its inhibitory action on EPSCs by acting at pre- and/or postsynaptic mechanisms. We examined the changes in PPR produced during DA application as an indication of pre- or postsynaptic mechanism. We found that bath application of DA greatly reduced the EPSCs but the inhibition was less on EPSC2 than on EPSC1 resulting in an increase in PPR, suggesting that DA acted presynaptically to reduce the probability of glutamate release from presynaptic terminals. We have also found that DA did not change membrane conductance nor that it affected the extrinsic glutamate-induced currents also arguing in favor of presynaptic mechanisms. This conclusion is also consistent with that of previous investigators studying DA inhibition on EPSCs in the nAcb as well as in the nucleus of the solitary tract, the subiculum, the supraoptic nucleus and the parabrachial nucleus. In other studies, DA has also been shown to produce postsynaptic effects in MS neurons but we and others failed to observe postsynaptic effects. In the present study, we added QX314 to the recording pipette solution in order to prevent voltage-sensitive Na + channels from generating action potentials. QX314 as well as other local anaesthetics have been shown to interfere with G protein-coupled receptors as well as with other second messenger systems and it is likely to have occluded the expression of dopaminergic postsynaptic effects. QX314 is also known to interfere with cholinergic muscarinic receptors. In a previous study we found that postsynaptic action mediated by muscarinic receptor was observed only when QX314 was omitted from the recording pipette. In addition, QX-314 is also known to inhibit Gprotein-gated K + conductances and this may have also occluded dopaminergic postsynaptic effects on K + conductance reported by others.