Interleukin-1beta (IL-1beta) is a pro-infiammatory cytokine that orchestrates infiammatory and host defense responses in the body. 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. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (alpha-MSH), through activation of MC4-R. The mechanisms underlying the effect of IL-1beta on memory reconsolidation have not been established yet. Thus, we examine the effect of IL-1beta on glutamate release, ERK2 phosphorylation and zif268 activation during reconsolidation. In this study, we demostrated that IL-1beta produces a signicant decrease of glutamate release after memory reactivation and also reduces ERK2 phosphorylation and zif268 expression in the hippocampus. The central administration of alpha-MSH can reverse the decrease of glutamate release and zif268 expression induced by IL-1beta. Our results 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.
