The present study examined the actions of a GABA(B)-receptor agonist, baclofen, on synaptic transmission in rat ventrolateral periaqueductal gray (PAG) neurons of brainstem slices by using whole-cell voltage-clamp recordings. Baclofen (10 muM) induced a slow outward Current (peak amplitude: 30.1 +/- 3.1 pA, n = 13) at -70 mV, which persisted in the presence of tetrodotoxin (0.5 muM) and was diminished in the presence of postsynaptic intracellular K+-channel blockers (Cs+ and TEA) and GDP-beta-S, indicating a direct postsynaptic depression mediated by K+ channels and G proteins. Baclofen (10 muM) also decreased the frequency of both glutamatergic spontaneous EPSC (by 36 +/- 7%, n = 11) and GABAergic spontaneous IPSC (by 37 +/- 12%, n = 6) without changes in their amplitudes, indicating its presynaptic inhibitions. Taken together, the activation of postsynaptic GABA(B) receptors inhibits ventrolateral PAG neurons directly. At the same time, activating presynaptic GABA(B) receptors on glutamatergic and GABAergic nerve terminals inhibits glutamate and GABA release, respectively. The overall effects might influence ail output of ventrolateral PAG neurons that build Lip the descending pain control system to the spinal dorsal horn. (C) 2003 Elsevier Science (USA). All rights reserved.