The effects of cytokines on cognitive processes have been extensively studied. Particularly, IL-1beta significantly influences consolidation of memories that depend on hippocampus. Concordantly, we previously reported that administration of IL-1beta in dorsal hippocampus impaired the consolidation of a contextual fear memory and that treatment with alpha-MSH blocked this effect. However, the mechanisms involved in the effect of IL-1beta on memory consolidation have not been established yet. It has been demonstrated that activation of p38 and Jun-kinase are involved in the inhibitory effect of LPS and IL-1beta on long term potentiation in vitro and that this effect was attenuated by an NF-kappaB inhibitor. Here we show that intrahippocampal injection of IL-1beta after training in a contextual fear paradigm induced a non-significant increase in p38 phosphorylation, indicating that this MAPK would not be involved in the effect of IL-1beta. Besides, western blot analysis demonstrated that IL-1beta induced a significant increase in nuclear NF-kappaB in dorsal hippocampus. We also observed that intrahippocampal injection of IL-1b after training induced a decreased in the glutamate release from dorsal hippocampus synaptosomes. The results are consistent with the idea that IL-1beta-induced impairment in memory consolidation could be mediated by a decreased in glutamate release. On the other hand, alpha-MSH administration did not modify NF-kappaB activation and glutamate levels induced by IL-1beta. Considering that alpha-MSH reversed the effect of IL-1beta on memory consolidation, and that alpha-MSH administration did not modify the effects of IL-1beta on the molecular mechanisms studied, further investigation is required to establish the signalling cascade involved in this modulation.
