BACKGROUNDIncreasing age was shown to decrease the requirements for propfol. However, the mechanisms of ageing-induced potentiation of anesthetic actions have not been clearly explored. The aim of this study is to compare the effects of propofol on the field excitatory postsynaptic potentials (fEPSPs) in hippocampal slices of young and aging mice.

METHODSBrain slices were prepared from C57BL6 male young (2 months) and aging (>12 months) mice. The dendritic field excitatory postsynaptic potential was recorded from the CA1 stratum radiatum using patch clamp electrophysiological methods. A bipolar concentric stimulating electrode was placed along the Schaffer collateral for othodromic stimulation. The effects of clinically-relevant concentrations of propofol were studied in the young and ageing mouse tissues.

RESULTSPropofol application increased the orthodromically evoked fEPSP produced in slices taken from young and older animals. A striking feature in the I/O relationship was the decreased enhancement of the fEPSPs by propofol in slices from older mice. A clinically relevant concentration of propofol, 10 µmol/L, showed more significant enhancement in amplitude and area under the curve (AUC) of fEPSP in young compared to tissues from older mice (amplitude: young (24.9 ± 3.4)%, old (4.6 ± 1.6)%; AUC young (30.6 ± 5.4)%, old (2.1 ± 1.7)%). There was no statistically significant difference between the paired-pulse facilitation (PPF) ratios calculated for the responses obtained in tissues from young mice. In slices from older mice, in the presence of 10 µmol/L propofol, PPF was decreased and returned to baseline after washout (baseline 1.21 ± 0.01, propofol: 1.16 ± 0.01). Bicuculline (15 µmol/L) blocked the enhancement of propofol on fEPSP in tissues from young and old mice.

CONCLUSIONThe fEPSP of slices from aging mice demonstrates diminished sensitivity to the enhancing actions of propofol.

Animals ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Excitatory Postsynaptic Potentials ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Propofol ; pharmacology