Small-dose pentobarbital enhances synaptic transmission in rat hippocampus

We investigated the contribution of bicarbonate ion, gamma -aminobutyric acid-A (GABA(A)) receptors, and N-methyl-D-aspartate (NMDA) receptors to pentobarbital-induced enhancement of excitatory synaptic transmission in the hippocampal slice. Transverse hippocampal slices (400 mum thick) were prepared from 20- to 30-day-old Sprague-Dawley rats and maintained in an interface chamber perfused with warmed (35 degreesC) oxygenated artificial cerebrospinal fluid. Extracellular field potentials, evoked by orthodromic paired-pulse stimulation of the Schaffer collateral CAI pathway, were analyzed for the population spike (PS) amplitude. Pentobarbital had a concentration-dependent, biphasic effect on PS amplitudes, which were increased approximately twofold (P < 0.001) when the slice was exposed to pentobarbital concentrations 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 was stopped during exposure to the drug. The enhancement of PS amplitude was suppressed in the presence of 10 muM acetazolamide, a nonselective carbonic anhydrase inhibitor, and when the slice was bathed in CO2/HCO3--free artificial cerebrospinal fluid. Pretreatment with 1 muM picrotoxin, a GABA(A) receptor antagonist, or 5 muM 2-amino-5-phosphopentanoic acid, a specific 1, A receptor antagonist, also suppressed enhancement of PS amplitude by 5 muM pentobarbital. The results suggest that small concentrations of pentobarbital (1 and 5 muM) enhance synaptic transmission through mechanisms involving GABA(A) and NMDA receptors and the HCO3- ion.