Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice.

Neuroscience Letters
Tolga UzRadmila Manev

Abstract

A common biological pathway may contribute to the comorbidity of atherosclerosis and depression. Increased activity of the enzymatic 5-lipoxygenase (5-LOX, 5LO) pathway is a contributing factor in atherosclerosis and a 5-LOX inhibitor, MK-886, is beneficial in animal models of atherosclerosis. In the brain, MK-886 increases phosphorylation of the glutamate receptor subunit GluR1, and the increased phosphorylation of this receptor has been associated with antidepressant treatment. In this work, we evaluated the behavioral effects of MK-886 in an automated assay of mouse forced swimming, which identifies antidepressant activity as increased climbing behavior and/or decreased rest time. Whereas a single injection of MK-886 (3 and 10 mg/kg) did not affect forced swimming behaviors assayed 30 min later, six daily injections of 3 mg/kg MK-886 slightly increased climbing and significantly reduced rest time in wild-type mice but not in 5-LOX-deficient mice. A diet delivery of MK-886, 4 micro/(100 mg(body-weight)day), required 3 weeks to affect forced swimming; it increased climbing behavior. Climbing behavior was also increased in naive 5-LOX-deficient mice compared to naive wild-type controls. These results suggest that 5-LOX inhibiti...Continue Reading

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Citations

Jun 23, 2010·PloS One·Hsiang-Chin ChenLoren W Runnels
Dec 29, 2009·Neuroscience Letters·Fabrício A PamplonaReinaldo N Takahashi
May 23, 2009·Toxicology and Applied Pharmacology·F RadognaL Ghibelli
Oct 10, 2015·Neuroscience Research·Stephanie Mijangos-MorenoEric Murillo-Rodríguez
May 7, 2019·Frontiers in Behavioral Neuroscience·Gisele A LocachevicLúcia H Faccioli
Jan 30, 2013·Journal of Psychiatric Research·Yash B Joshi, Domenico Praticò
Oct 10, 2020·Free Radical Biology & Medicine·Kalpana Kumari BarhwalSunil Kumar Hota
Aug 13, 2021·Frontiers in Cell and Developmental Biology·Teng ZhangQing Tian

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