The effect of forskolin on corticostriatal synaptic transmission was examined by recording excitatory postsynaptic currents (EPSCs) in rat brain slices using the whole-cell voltage-clamp technique. Forskolin produced a dose-dependent increase of corticostriatal EPSCs (1, 3, 10, and 30ՌM) immediately after its treatment, and the increase at 10 and 30ՌM was maintained even after its washout. When the brain slices were pre-treated with <FONT SIZE=2>(DL)-2-amino-5-phosphonovaleric acid (AP-V, 100ՌM), an NMDA receptor antagonist, the acute effect of forskolin (10ՌM) was blocked. However, after washout of forskolin, an increase of corticostriatal EPSCs was still observed even in the presence of AP-V. When KT 5720 (5ՌM), a protein kinase A (PKA) inhibitor, was applied through the patch pipette, forskolin (10ՌM) increased corticostriatal EPSCs, but this increase was not maintained. When forskolin was applied together with AP-V and KT 5720, both the increase and maintenance of the corticostriatal EPSCs were blocked. These results suggest that forskolin activates both NMDA receptors and PKA, however, in a different manner.