Memory impairment induced by IL-1β is reversed by α-MSH through central melanocortin-4 receptors |
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Authors: | Patricia Vernica Gonzalez Helgi Birgir Schith Mercedes Lasaga Teresa Nieves Scimonelli |
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Institution: | aIFEC CONICET Departamento de Farmacología, Facultad de Ciencias Químicas, Haya de la Torre y Medina Allende, Ciudad Universitaria, UNC, 5000 Córdoba, Argentina;bDepartment of Neuroscience, Uppsala University, Uppsala, Sweden;cCentro de Investigaciones en Reproducción, Facultad de Medicina, UBA, Buenos Aires, Argentina |
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Abstract: | Interleukin-1beta (IL-1β) significantly influences memory consolidation. Treatments that raise the level of IL-1β in the brain, given after training, impair contextual fear conditioning. The melanocortin α-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-1β (5 ng/0.25 μl) in dorsal hippocampus up to 15 min after training decreased freezing during the contextual fear test. The treatment with IL-1β (5 ng/0.25 μl) 12 h after conditioning cause amnesia when animals were tested 7 days post training. Thus, our results also demonstrated that IL-1β can influence persistence of long-term memory. We determined that animals previously injected with IL-1β can acquire a new contextual fear memory, demonstrating that the hippocampus was not damaged. Treatment with α-MSH (0.05 μg/0.25 μl) blocked the effect of IL-1β on contextual fear memory. Administration of the MC4 receptor antagonist HS014 (0.5 μg/0.25 μl) reversed the effect of α-MSH. However, treatment with γ-MSH (0.5 μg/0.25 μl), an MC3 agonist, did not affect IL-1β-induced impairment of memory consolidation. These results suggest that α-MSH, through central MC4R can inhibit the effect of IL-1β on memory consolidation. |
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Keywords: | Interleukin-1beta Melanocortins Melanocortin receptors Fear conditioning Memory consolidation Memory persistence Hippocampus |
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