Involvement of synaptic transmission in the actions of general anesthetics in rat hippocampal slices in vitro

It has been uncertain whether general anesthetics act through the synaptic transmission or directly act on the neural membrane in the central nervous systems (CNS). In the present study we have investigated the effects of general anesthetics on field population spikes (PSs) evoked with stimulation of either the Schaffer collateral fiber input to CA1 pyramidal neurons (orthodromic mono-synaptic pathway) or the alveus hippocampi input to CA1 (antidromic non-synaptic pathway). Volatile anesthetics (halothane, isoflurane) reduced the PS amplitudes with orthodromic stimuli (Orth-PS), remaining the antidromically evoked PSs (Anti-PS) unchanged. On the other hand, ketamine inhibited both Orth-PS and Anti-PS. The results indicated that volatile anesthetics act through the synaptic transmission, while ketamine directly acts on the neural membrane as well as on the synaptic transmission, and that mechanisms by which general anesthetics inhibit neural excitability could be agent-and pathway-specific.