Small-dose pentobarbital enhances synaptic transmission in rat hippocampus

We investigated the contribution of bicarbonate ion, gamma -aminobutyric ac id-A (GABA(A)) receptors, and N-methyl-D-aspartate (NMDA) receptors to pent obarbital-induced enhancement of excitatory synaptic transmission in the hi ppocampal slice. Transverse hippocampal slices (400 mum thick) were prepare d from 20- to 30-day-old Sprague-Dawley rats and maintained in an interface chamber perfused with warmed (35 degreesC) oxygenated artificial cerebrosp inal fluid. Extracellular field potentials, evoked by orthodromic paired-pu lse stimulation of the Schaffer collateral CAI pathway, were analyzed for t he population spike (PS) amplitude. Pentobarbital had a concentration-depen dent, biphasic effect on PS amplitudes, which were increased approximately twofold (P < 0.001) when the slice was exposed to pentobarbital concentrati ons of I and 5 muM and depressed at drug concentrations larger than 10 muM. Pentobarbital (5 muM) did not increase the PS amplitude when stimulation w as stopped during exposure to the drug. The enhancement of PS amplitude was suppressed in the presence of 10 muM acetazolamide, a nonselective carboni c anhydrase inhibitor, and when the slice was bathed in CO2/HCO3--free arti ficial cerebrospinal fluid. Pretreatment with 1 muM picrotoxin, a GABA(A) r eceptor antagonist, or 5 muM 2-amino-5-phosphopentanoic acid, a specific 1, A receptor antagonist, also suppressed enhancement of PS amplitude by 5 mu M pentobarbital. The results suggest that small concentrations of pentobarb ital (1 and 5 muM) enhance synaptic transmission through mechanisms involvi ng GABA(A) and NMDA receptors and the HCO3- ion.