It has been described that the immune activation causes deficits in learning and memory. Interleukin-1beta (IL-1beta), a potent pro-inflammatory cytokine, has deleterious effects on memory consolidation. The melanocortin alpha-MSH exerts potent anti-inflammatory actions by antagonizing the effect of proinflammatory 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-1beta (5ng) in dorsal hippocampus immediately after training decreases freezing during the contextual fear conditioning test. Treatment with alpha-MSH (0.05ug) blocked this effect. Administration of the MC4 receptor antagonist HS014 (0.5ug) reverses the effect of alpha-MSH. However, the treatment with alpha-MSH, an MC3 agonist, did not affect the IL-1beta-induced impairment of memory consolidation. Our results also showed that IL-1beta can modulate the persistence of memory. These results suggest that alpha-MSH, through MC4R may inhibit the effect of IL-1beta on memory consolidation.
