The NAc mediates many aspects of drug addiction including sensitization, withdrawal and self-administration. DA D1 and D2 class receptors modulate medium spiny neurons of NAc. Although this modulation has received considerable attention, the mechanism underlying D2R-mediated alterations in neuronal activity is poorly understood. In the present study, we performed whole-cell current-clamp recordings in rat brain slices to determine the effects of D2R stimulation on the activity of medium spiny neurons located within the core of NAc. Our results reveal that D2R stimulation by quinpirole (10 mM) suppresses sodium-dependent action potentials evoked by injection of depolarizing current pulses. This reduction of evoked spikes was associated with an increase in the current required for generation of spikes (reobase). This effect of quinpirole on evoked spikes was completely blocked by concurrent application of eticlopride (10 mM), a D2R antagonist. In addition, blocking A-type potassium currents with a low concentration of 4-aminopyridine (4-AP, 10 mM) reversed the reduction of evoked spikes induced by D2R stimulation. Moreover, when membrane potential was held at ?50 mV, the ability of D2R stimulation to suppress evoked spikes was eliminated. These findings suggest that D2R stimulation may enhance slowly-inactivating A-type potassium currents in NAc neurons in a membrane potential dependent manner.
