Effects of isoflurane and thiopental on synaptic potentials in hippocampal slices of the rat

In order to assess the mechanism(s) of general anesthetics in the central nervous system, we studied the effects of isoflurane and thiopental on synaptic potentials of Schaffer collateral fibers input to CA1 pyramidal neurons in rat hippocampal slices. Transverse hippocampal slices (400 μm) were obtained from male Wistar rats (100-200 g) by standard methods. Field excitatory postsynaptic potentials (EPSPs) and population spikes (PSs) were elicited with a bipolar nichrome electrode placed on Schaffer collateral fibers and were recorded at area CA1 with a glass-microelectrode. Isoflurane was vaporized with a isoflurane vaporizer and then bubbled into ACSF. Thiopental was directly dissolved into ACSF. Isoflurane (0.5 to 5.0 vol%) and thiopental (10^-5 to 5 x 10^-4 M) decreased the PS amplitudes in a dose-dependent manner without a change in EPSP slopes. Paired-pulse experiments revealed that isoflurane (2.0 vol%) significantly enhanced the paired-pulse facilitation (PPF) and that thiopental (2 x 10^-4 M) markedly reduced the PPF. The observed effects of thiopental were blocked with GABA(A) receptor antagonist, bicuculline (5 μM). However, bicuculline (5 μM) failed to completely block the actions of isoflurane. We concluded (a) that GABA(A) ergic modulations are responsible for the thiopental depressions on PS amplitudes in area CA1 of hippocampus and (b) that additional factors may be involved in the actions of isoflurane.