title: Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.
abstract: We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014.
authors.affiliation: Instituto de Biotecnología, Centro de Investigación e Innovación Tecnológica (CENIIT), Universidad Nacional de La Rioja, La Rioja, Argentina.
authors.forename: Carlos Horacio
authors.initials: CH
authors.lastname: Laino
authors.forename: Pilar
authors.initials: P
authors.lastname: Garcia
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Podestá
authors.forename: Christian
authors.initials: C
authors.lastname: Höcht
authors.forename: Nora
authors.initials: N
authors.lastname: Slobodianik
authors.forename: Analía
authors.initials: A
authors.lastname: Reinés
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D015525:Fatty Acids, Omega-3; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; C036139:norfluoxetine
keywords: antidepressants; depression; drug effects; drug-like properties; fluoxetine; forced swimming test; omega-3 fatty acids; pharmacodynamic; physiological model; preclinical pharmacokinetic