gamma-hydroxybutyrate inhibits excitatory postsynaptic potentials in rat hippocampal slices

gamma-Hydroxybutyrate (GHB) has been shown to mimic different central actio ns of ethanol, to suppress alcohol withdrawal syndrome, and to reduce alcoh ol consumption both in rats and in humans. The aim of the present study was to determine if GHB shared with alcohol the ability to inhibit glutamate a ction at both NMDA and AMPA/kainate receptors. The NMDA or the AMPA/kainate receptors-mediated postsynaptic potentials were evoked in CA1 pyramidal ne urons by stimulation of Schaffer-collateral commissural fibers in the prese nce of CGP 35348, bicuculline to block the GABA(B) and GABA(A) receptors, a nd 10 mu M 6,7-dinitroquinoxaline-2,3-dione (DNQX) or 30 mu M DL-2-amino-5- phosphonovalerate (d-APV) to block AMPA/kainate or NMDA receptors, respecti vely. GHB (600 mu M) produced a depression of both NMDA and AMPA/kainate re ceptors-mediated excitatory postsynaptic potentials with recovery on washou t. The GHB receptors antagonist, NCS-382, at the concentration of 500 mu M had no effect per se on these responses but prevented the depressant effect of GHB (600 mu M) on the NMDA and AMPA/kainate-mediated responses. In the paired-pulse experiments, GHB (600 mu M) depressed the amplitude of the fir st and the second evoked AMPA/kainate excitatory postsynaptic potentials, a nd significantly increased the paired-pulse facilitation (PPF). These resul ts suggest that GHB inhibits excitatory synaptic transmission at Schaffer-c ollateral commissural-pyramidal neurons synapses by decreasing the probabil ity of release of glutamate. (C) 1999 Elsevier Science B.V, All rights rese rved.