In pyramidal cells from rat prefrontal cortex, Dopamine (DA) modulates the response of excitatory synaptic inputs to repetitive presynaptic activation (Seamans et al. PNAS 2001). To examine whether DA also modulates EPSP dynamics in local circuits of layers 2/3 in monkey dorsolateral prefrontal cortex (areas 9 and 46), we examined the effects of DA on trains of EPSPs recorded from Fast Spiking (FS) interneurons. As we reported previously (SFN 2001 Abstr 729.15), during 20 Hz-10 stimulus trains, EPSPs in FS cells depress with little temporal summation. DA (10-50 µM) or D1 agonists (SKF81297 or SKF38393, 10 µM) reduced the amplitude of the first EPSP in the trains (EPSP(1)) and increased the EPSP(10)/EPSP(1) ratio, apparently reducing depression. Decreasing probability of release by reducing the external Ca2+/Mg2+ ratio also reduced EPSP(1) amplitude but only partially mimicked the increase in EPSP(10)/EPSP(1) ratio by DA. A higher EPSP(10)/EPSP(1) ratio could be mediated by modulation of NMDA currents, sinc...