We previously reported that administration of IL-1beta in dorsal hippocampus impairs the consolidation of a contextual fear memory. Treatment with alpha-MSH blocked this effect. However, the mechanisms involved in the cytokines effect 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 LTP in vitro. Also, this effect was attenuated by a NF-kappaB inhibitor. The present experiments show that intrahippocampal injection of IL-1beta after training in a contextual fear paradigm induced a decrease in glutamate release from dorsal hippocampus. alpha-MSH administration (0.05ug) did not reverse this effect. The inhibitory effect of IL-1beta on memory consolidation was not reversed by the NF-kappaB inhibitor SN50 (20ug). However, western blot analysis demonstrated that IL-1beta induces a significant increase in nuclear NF-kappaB in dorsal hippocampus. Probably, as described before, astrocytes are the source of the increase in NF-kappaB, and so, this effect was not involved in memory consolidation. Preliminary results show that the inhibition of p38 by SB203580 (100mM) reduced the effect of IL-1beta on memory consolidation. The results are consistent with the idea that IL-1beta-induced impairment in memory consolidation is mediated by a decrease in glutamate released and p38 MAPK activation in dorsal hippocampus.
