Inhibition of NMDA receptor-mediated synaptic transmission in the rat dentate gyrus in vitro by IL-1 beta

THE action of interleukin-1 beta (IL-1 beta) and its receptor antagonist IL-1ra were investigated on dual component, isolated AMPA and NR IDA field excitatory postsynaptic potentials (EPSP) and on the induction and maintenance of long-term potentiation in the rat dentate gyrus in vitro. Perfusion with IL-1 beta (1 ng/ml) for Ih had no significant effect on the dual component EPSP or the isolated AMPA-EPSP. In contrast IL-1 beta had a significant inhibitory effect on the isolated NMDA-EPSP amplitude (54 +/- 7% at Ih compared with controls; n = 9; p < 0.001). This effect was fully antagonized in the presence of 100 ng/ml IL-1 receptor antagonist. IL-1 beta also inhibited LTP of the dual component EPSP but had no effect on the maintenance phase when applied postinduction of LTP. This study demonstrates for the first time that the inhibitory effect of IL-1 beta on LTP in the dentate gyrus may be at least partially due to a block of post-synaptic NMDA receptors.