Previous studies of our group have demonstrated that the intrahippocampal administration of IL-1beta impairs 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 yet been established. Thus, we examined the effect of IL-1beta on glutamate release, cytosolic calcium influx and ERK phosphorylation during reconsolidation. Our results demonstrated that IL-1beta produced a decrease in glutamate release after reactivation of a contaxtual fear memory. IL-1beta also reduced ERK phosphorylation in the hippocampus. The central administration of the alpha-MSH can reverse both the decrease of glutamate release and ERK phosphorylation induced by IL-1beta. We establish 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.
