It has been described that the immune activation causes deficits in learning and memory. Interleukin-1beta (IL-1b), a potent pro-inflammatory cytokine, has deleterious effects on memory consolidation. The melanocortin a-MSH exerts potent anti-inflammatory actions by antagonizing the effect of pro-inflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, being the MC3R and MC4R predominant in the central nervous system. The present experiments show that the bilateral injection of IL-1b (5 ng) in dorsal hippocampus immediately after training decreases freezing during the contextual fear conditioning test. The treatment with a-MSH (0.05mg) blocked this effect. Administration of the MC4 receptor antagonist HS014 (0.5 mg) reverses the effect of a-MSH. However, the treatment with g-MSH, an MC3 agonist, did not affect the IL-1b-induced impairment of memory consolidation. Our results also demonstrated that IL-1b can modulate the persistence of memory. These results suggest that a-MSH, through MC4R activation can inhibit the effect of IL-1b on memory consolidation.
