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Epidemiological and dietary studies show that nutritional deficit of omega-3 polyunsaturated fatty acids (ω-3 PUFA) is directly related to the prevalence and severity of depression. Supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) during critical periods of development (pregnancy and lactation) is essential for cortical maturation, synaptogenesis and myelination, and may also mitigate the risk for cognitive deficits and psychopathologies in young adults. The present study was performed to evaluate the involvement of serotonin (5-HT) receptors, particularly of 5-HT(1A), and hippocampal brain-derived neurotrophic factor (BDNF) expression in the antidepressant effect of ω-3 PUFA supplementation. In Experiment 1, the antidepressant effects of fish oil were assessed by the modified forced swim test in adult rats. The data indicated a robust antidepressant effect produced by this supplementation and that treatment of the rats with WAY 100135 reversed this effect. In Experiment 2, cortical and hippocampal contents of BDNF, 5-HT, dopamine (DA) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), and 3,4-dihydroxyphenylacetic acid (DOPAC), were determined in animals subjected to the same protocol. Increased BDNF expression in the cortex and hippocampus of both age groups was detected. In 90 day-old rats, 5-HT content in the hippocampus was increased, whereas 5-HIAA formation was diminished in the fish oil group. We suggest the occurrence of a reciprocal involvement of 5-HT(1A) receptors activation and the hippocampal BDNF-increased expression mediated by fish oil supplementation. These data corroborate and expand the notion that supplementation with ω-3 PUFA produces antidepressant effects mediated by an increase in serotonergic neurotransmission, particularly in the hippocampus. This article is part of a Special Issue entitled 'Anxiety and Depression'. Copyright © 2011 Elsevier Ltd. All rights reserved.


Aparecida Vines, Ana Marcia Delattre, Marcelo M S Lima, Laís Soares Rodrigues, Deborah Suchecki, Ricardo B Machado, Sergio Tufik, Sofia I R Pereira, Sílvio M Zanata, Anete Curte Ferraz. The role of 5-HT₁A receptors in fish oil-mediated increased BDNF expression in the rat hippocampus and cortex: a possible antidepressant mechanism. Neuropharmacology. 2012 Jan;62(1):184-91

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PMID: 21740919

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