Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors

PATRICIA VERÓNICA GONZALEZ; HELGI BIRGIR SCHIÖTH; MERCEDES LASAGA; TERESA NIEVES SCIMONELLI

BRAIN BEHAVIOR AND IMMUNITY

Elsevier

Año: 2009 vol. 23 p. 817 - 822

0889-1591

Interleukin-1beta (IL-1b) significantly influences memory consolidation. Treatments that raise the level of IL-1b in the brain, given after training, impair contextual fear conditioning. The melanocortin a-MSH exerts potent anti-inflammatory actions by physiologically antagonizing the effect of pro-inflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, with MC3R and MC4R predominating in the central nervous system. The present experiments show that injection of IL-1b (5ng/0.25ml) in dorsal hippocampus up to 15 min after training decreased freezing during the contextual fear test. The treatment with IL-1b (5ng/0.25ml) 12hs after conditioning cause amnesia when animals were tested 7 days post training. Thus, our results also demonstrated that IL-1b can influence persistence of long-term memory. We determined that animals previously injected with IL-1b can acquire a new contextual fear memory, demonstrating that the hippocampus was not damaged. Treatment with a-MSH (0.05mg/0.25ml) blocked the effect of IL-1b on contextual fear memory. Administration of the MC4 receptor antagonist HS014 (0.5mg/0.25ml) reversed the effect of a-MSH. However, treatment with g-MSH (0.5mg/0.25ml), an MC3 agonist, did not affect IL-1b-induced impairment of memory consolidation. These results suggest that a-MSH, through central MC4R can inhibit the effect of IL-1b on memory consolidation