Ketamine blocks an NMDA receptor-mediated component of synaptic transmission in rat hippocampus in a voltage-dependent manner.

We have examined the voltage dependence of the effects of ketamine on synaptic currents in hippocampal CA1 neurons in vitro under conditions where there is a large N-methyl-D-aspartate (NMDA) receptor mediated component of the response. Ketamine reduced inward currents to a greater extent than outward currents of a corresponding size. D-2-Amino-5-phosphonovalerate (APV) substantially reduced the residual outward currents recorded in ketamine, but had only a small effect on the residual inward ones. It is concluded that in this system the action of ketamine in blocking synaptically evoked NMDA receptor-mediated currents shows some voltage dependence.