Sevoflurane modulates both GABAA and GABAB receptors in area CA1 of rat hippocampus

It has been suggested that volatile anaesthetics enhance synaptic inhibition via gamma-aminobutyric acid (GABA) in the central nervous system. We have examined the effects of sevoflurane on GABAA and GABAB receptors in rat hippocampus in vitro. Extracellular recordings were used to record field potentials in rat CA1 pyramidal neurones of transverse hippocampal slices, stimulated electrically via stratum radiatum input. Sevoflurane 0.4-5.0 vol% decreased the amplitudes of population spikes (PS) of CA1 neurones in a concentration-dependent (calculated ED50 = 6.31 vol%) and reversible manner. The GABAA antagonist, bicuculline methiodide 5 x 10(-5) mol litre-1, induced oscillations (multiple spikes) and blocked the inhibitory actions of sevoflurane in the initial component (up to 24.8 ms) of the oscillation. The latter portion of the oscillation (greater than 24.8 ms) was depressed by sevoflurane. The GABAB antagonist, phaclofen 5 x 10(-4) mol litre-1 partially blocked the effects of sevoflurane on the latter portion of the bicuculline-induced oscillation. Sevoflurane 2.0 vol% significantly enhanced paired-pulse (PS2/PS1) facilitation (from 128.4% to 155.5% at an inter-stimulus interval of 37.9 ms); this enhancement was blocked by phaclofen. Stimulus-response relationships revealed that 2.0 vol% sevoflurane increased the intensity of threshold for PS generation to 109.8% of control. Both the GABAA agonist, muscimol 2 x 10(-5) mol litre-1 and the GABAB agonist, (+/-)-baclofen 10(-5) mol litre-1, potentiated the effects of sevoflurane. Sevoflurane enhanced thresholds by 137.1% and 138.5% of control in the presence of muscimol and (+/-)-baclofen, respectively. The results demonstrate that sevoflurane at clinical concentrations activated both GABAA- and GABAB-mediated inhibitions in area CA1 of the hippocampus, and that sevoflurane and GABA agonists (muscimol and baclofen) acted on different domains on the GABAA and GABAB receptors, respectively.