Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that orchestrates inflammatory and host defense responses. Apart from this role, IL-1beta has also been implicated in cognitive processes. Previous studies of our group have demonstrated that the intrahippocampal administration of IL-1beta impaired reconsolidation of contextual fear memory. The melanocortin α-melanocyte- stimulating hormone (alpha-MSH) exerts potent anti-inflammatory actions by antagonizing the effect of proinflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, of which MC3R and MC4R are predominant in the central nervous system. In previous work, we have shown that the effect of IL-1beta was reversed by alpha-MSH through the activation of MC4-R. The mechanisms underlying the effect of IL-1beta and alpha-MSH on memory reconsolidation have not been established yet. We find that memory reconsolidation induces an increase in glutamate release, ERK2 phosphorylation and zif268 expression. After the reactivation of a contextual fear memory the administration of IL-1beta produces a decrease in glutamate release, ERK2 phosphorylation and a reduction in zif268 expression. We also show that alpha-MSH reverses the effect of IL-1beta on glutamate release and zif268 expression. Our results suggest that memory reconsolidation impairment induced by IL-1beta could be mediated by a decrease in glutamate release, a reduction in ERK2 phosphorylation and zif268 expression. Alpha-MSH reverses the effect of IL-1beta on memory reconsolidation. In this study, we establish for the first time the possible mechanisms involved in the detrimental effect of IL-1beta on memory reconsolidation and also that alpha-MSH may exert a beneficial modulatory role in preventing IL-1beta effects.
