title: Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors.
abstract: Interleukin-1beta (IL-1beta) significantly influences memory consolidation. Treatments that raise the level of IL-1beta in the brain, given after training, impair contextual fear conditioning. The melanocortin alpha-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-1beta (5 ng/0.25 microl) in dorsal hippocampus up to 15 min after training decreased freezing during the contextual fear test. The treatment with IL-1beta (5 ng/0.25 microl) 12h after conditioning cause amnesia when animals were tested 7 days post training. Thus, our results also demonstrated that IL-1beta can influence persistence of long-term memory. We determined that animals previously injected with IL-1beta can acquire a new contextual fear memory, demonstrating that the hippocampus was not damaged. Treatment with alpha-MSH (0.05 microg/0.25 microl) blocked the effect of IL-1beta on contextual fear memory. Administration of the MC4 receptor antagonist HS014 (0.5 microg/0.25 microl) reversed the effect of alpha-MSH. However, treatment with gamma-MSH (0.5 microg/0.25 microl), an MC3 agonist, did not affect IL-1beta-induced impairment of memory consolidation. These results suggest that alpha-MSH, through central MC4R can inhibit the effect of IL-1beta on memory consolidation.
authors.affiliation: IFEC CONICET Departamento de Farmacología, Facultad de Ciencias Químicas, Haya de la Torre y Medina Allende, Ciudad Universitaria, UNC, Córdoba, Argentina. vgonzalez@fcq.unc.edu.ar
authors.forename: Patricia Verónica
authors.initials: PV
authors.lastname: Gonzalez
authors.forename: Helgi Birgir
authors.initials: HB
authors.lastname: Schiöth
authors.forename: Mercedes
authors.initials: M
authors.lastname: Lasaga
authors.forename: Teresa Nieves
authors.initials: TN
authors.lastname: Scimonelli
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D005239:Fear / Q000523:psychology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3 / Q000187:drug effects; D044105:Receptor, Melanocortin, Type 4 / Q000187:drug effects*; D000521:alpha-MSH / Q000494:pharmacology*; D019825:gamma-MSH / Q000494:pharmacology
chemical_list: D053583:Interleukin-1beta; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D019825:gamma-MSH; D000521:alpha-MSH