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Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
2009 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 23, no 6, 817-822 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 23, no 6, 817-822 p.
Keyword [en]
Interleukin-1 beta, Melanocortins, Melanocortin receptors, Fear conditioning, Memory consolidation, Memory persistence, Hippocampus
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-124761DOI: 10.1016/j.bbi.2009.03.001ISI: 000268304800014PubMedID: 19275930OAI: oai:DiVA.org:uu-124761DiVA: diva2:317939
Available from: 2010-05-05 Created: 2010-05-05 Last updated: 2010-07-16Bibliographically approved

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