TY - JOUR T1 - Multiple Actions of Methohexital on Hippocampal CA1 and Cortical Neurons of Rat Brain Slices JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1177 LP - 1182 VL - 286 IS - 3 AU - Liang Zhang AU - Yu Zhang AU - Richard Wennberg Y1 - 1998/09/01 UR - http://jpet.aspetjournals.org/content/286/3/1177.abstract N2 - To explore the mechanism by which methohexital (MTH) activates epileptiform activity in patients with epilepsy, we examined the effects of MTH on hippocampal CA1 and neocortical neuronsvia extracellular and whole-cell patch-clamp recordings in rat brain slices. Perfusion of slices with 10 to 100 μM MTH caused no significant change in glutamatergic transmission in the hippocampal CA1 region, but enhanced γ-aminobutyric acid (GABA)A-mediated inhibitory postsynaptic currents and induced spontaneous inhibitory postsynaptic currents in neocortical and hippocampal CA1 neurons. In addition, MTH induced a tonic, bicuculline-sensitive hyperpolarization in association with increases in membrane conductance, suggesting a direct stimulation of GABAA receptors by MTH. Spontaneous epileptiform activity was not observed in the neocortex and hippocampus after exposure of slices to MTH, neither in the standard in vitrocondition nor in the presence of 4-aminopyridine, which promotes rhythmic synaptic activities. We suggest that the activation of epileptiform activity in vivo by MTH may result from increased neuronal synchrony via the potentiation of GABAA-mediated synaptic inhibition. The American Society for Pharmacology and Experimental Therapeutics ER -