Dopamine depresses excitatory and inhibitory synaptic transmission by distinct mechanisms in the nucleus accumbens.

The release of dopamine (DA) in the nucleus accumbens (NAc) is thought to be critical for mediating natural rewards as well as for the reinforcing actions of drugs of abuse. DA and amphetamine depress both excitatory and inhibitory synaptic transmission in the NAc by a presynaptic D1-like DA receptor. However, the mechanisms of depression of excitatory and inhibitory synaptic transmission appear to be different. DA depressed the frequency of spontaneous miniature EPSCs, but the frequency of miniature IPSCs was depressed only when spontaneous release was made dependent on Ca2+ influx through voltage-dependent Ca2+ channels. Furthermore, the K+ channel blocker Ba2+ attenuated the effects of DA on evoked IPSPs, but not on EPSPs. Thus, DA appears to depress inhibitory synaptic transmission in the NAc by reducing Ca2+ influx into the presynaptic terminal, but depresses excitatory transmission by a distinct mechanism that is independent of the entry of Ca2+.