Hippocampal in vitro kindling is not blocked by nitric oxide synthase inhibitors.

Effects of nitric oxide synthase (NOS) inhibitors on the induction of an in vitro model of kindling were investigated in the rat hippocampal slice. It has been reported that NMDA receptor activation stimulates NOS and guanosine 3',5'-cyclic monophosphate (cGMP) production and that the interruption of this pathway interferes with LTP in the CA1 hippocampal field. Because the induction of LTP and kindling both involve NMDA receptor activation, we tested the effects of NOS inhibitors on the genesis and initial rate of interictal-like spontaneous bursts in CA1 and CA3 of the rat hippocampal slice. Experimental groups were exposed to 100 microM methyl-L-arginine (active NOS inhibitor), nitro-L-arginine (active NOS inhibitor), or methyl-D-arginine (inactive isomer of the NOS inhibitor) for 1 h prior to in vitro kindling. These results indicate that rather than preventing the induction of kindling in this model of epileptogenesis, NOS inhibition may facilitate the initiation of interictal-like spontaneous bursts in the rat hippocampal slice.