Does propofol enhance GABA-mediated inhibition?

Abstract

The effects of propofol on synaptic transmission were characterized and compared with pentobarbital in the rat hippocampal slice preparation. Hippocampal CA1 population spike after stimulation of Schaffer collaterals indicated that the postsynaptic response was primarily mediated by non-N-methyl-D-aspartate class glutamate receptors since it was abolished by the presence of 6,7-dinitroquinoxaline-2,3-dione (DNQX). Propofol and pentobarbital depressed CA1 population spike amplitude in a dose dependent fashion. Dose-response curves for population spike amplitudes were determined for propofol and pentobarbital and the concentrations producing a half-maximum response (ED(50)) were 110 microM and 160 microM for propofol and pentobarbital, respectively. By contrast, when GABA A-mediated inhibition was blocked by addition of 100 microM pictotoxin, propofol, in concentrations up to 400 microM had no significant effect on population spike amplitudes. These results suggest that propofol attenuates synaptic transmission in the central nervous system in part by enhancing GABA A-mediated inhibition and not by depressing glutamate-mediated excitation, as occurs with pentobarbital.