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THE action of interleukin-1[beta] (IL-1[beta]) and its receptor antagonist IL-1ra were investigated on dual component, isolated AMPA and NMDA 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 1 h 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 1 h 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.

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