α-Melanocyte-stimulating hormone (α-MSH) reverses impairment of memory reconsolidation induced by interleukin-1 beta (IL-1 beta) hippocampal infusions

Interleukin-1 beta (IL-1β) significantly influences cognitive processes. Treatments which raise the level of IL-1β in the brain impair memory consolidation in contextual fear conditioning. However, the effect of IL-1β on memory reconsolidation has not yet been established. The melanocortin α-melanocyte-stimulating hormone (α-MSH) exerts potent anti-inflammatory actions by antagonizing the effect of proinflammatory cytokines. Five subtypes of melanocortin receptors (MC1R–MC5R) have been identified, of which MC3R and MC4R are predominant in the central nervous system. The present experiments show that the injection of IL-1β (5 ng/0.25 μl) in dorsal hippocampus up to 30 min after re-exposition to the context decreases freezing during the contextual fear test. Impairment of memory reconsolidation was reversed by treatment with α-MSH (0.05 μg/0.25 μl). Administration of the MC4 receptor antagonist HS014 (0.5 μg/0.25 μl) blocked the effect of α-MSH. These results suggest that IL-1β may influence memory reconsolidation and that activation of central MC4R could lead to improve cognitive performance.

Research highlights▶ IL-1β has a detrimental effect on reconsolidation of contextual memory. ▶ Memory impairment induced by IL-1β is reversed by α-MSH. ▶ α-MSH may exert this protective effect by activating brain MC4-R.