The immune system plays a central role in modulating learning, memory and neural plasticity. Interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, significantly affects several cognitive processes. 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 Ca2 dependent glutamate release and zif268 activation during reconsolidation. Here we found that IL-1beta produced a significant decrease in glutamate release after reactivation of the fear memory and also reduced zif268 expression in the hippocampus. The central administration of the melanocortin 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 benefitial modulatory role in preventing IL-1beta effects.
