The Antidepressant-Like Effect of Fish Oil: Possible Role of Ventral Hippocampal 5-HT1A Post-synaptic Receptor

• Published in: Molecular neurobiology 2015-08, Vol.52 (1), p.206-215
• Main Authors: Carabelli, Bruno, Delattre, Ana Marcia, Pudell, Claudia, Mori, Marco Aurélio, Suchecki, Deborah, Machado, Ricardo B., Venancio, Daniel Paulino, Piazzetta, Sílvia Regina, Hammerschmidt, Ivilim, Zanata, Sílvio M., Lima, Marcelo M. S., Zanoveli, Janaína Menezes, Ferraz, Anete Curte
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cell Biology; Chromatography, High Pressure Liquid; Female; Fish Oils - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Immobilization; Male; Neurobiology; Neurology; Neurosciences; Rats, Wistar; Receptor, Serotonin, 5-HT1A - metabolism; Swimming; Synapses - drug effects; Synapses - metabolism
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-014-8849-8

The pathophysiology of depression is not completely understood; nonetheless, numerous studies point to serotonergic dysfunction as a possible cause. Supplementation with fish oil rich docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) during critical periods of development produces antidepressant effects by increasing serotonergic neurotransmission, particularly in the hippocampus. In a previous study, the involvement of 5-HT 1A receptors was demonstrated and we hypothesized that fish oil supplementation (from conception to weaning) alters the function of post-synaptic hippocampal 5-HT 1A receptors. To test this hypothesis, female rats were supplemented with fish oil during habituation, mating, gestation, and lactation. The adult male offspring was maintained without supplementation until 3 months of age, when they were subjected to the modified forced swimming test (MFST) after infusion of vehicle or the selective 5-HT 1A antagonist, WAY100635, and frequency of swimming, immobility, and climbing was recorded for 5 min. After the behavioral test, the hippocampi were obtained for quantification of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and for 5-HT 1A receptor expression by Western blotting analysis. Fish oil-supplemented offspring displayed less depressive-like behaviors in the MFST reflected by decreased immobility and increased swimming and higher 5-HT hippocampal levels. Although there was no difference in the expression of hippocampal 5-HT 1A receptors, intra-hippocampal infusion of a sub-effective dose of 8-OH-DPAT enhanced the antidepressant effect of fish oil in supplemented animals. In summary, the present findings suggest that the antidepressant-like effects of fish oil supplementation are likely related to increased hippocampal serotonergic neurotransmission and sensitization of hippocampal 5-HT 1A receptors.