The whole-cell configuration of the patch clamp technique was used to study the effect of an intracellular increase in cAMP on the frequency of GABA-mediated miniature post synaptic currents (MPSCs) in neonatal rats from (P6 to P12) CA3 hippocampal neurons in slices. In the presence of tetrodotoxin (1 microM), and kynurenic acid (1 mM) to block ionotropic glutamatergic currents, forskolin, an activator of adenylate cyclase, markedly increased the frequency of MPSCs without affecting their amplitude or kinetics. The inactive forskolin analog, 1,9-dideoxyforskolin (30 microM), had no effect on the frequency of MPSCs. The effect of forskolin was prevented by the specific protein kinase A (PKA) antagonist Rp-cAMP (30 microM). It is concluded that stimulation of PKA potentiates spontaneous GABA release in immature hippocampal neurons.