Document Detail


Effect of chronic fluoxetine treatment on male and female rat erythrocyte and prefrontal cortex fatty acid composition.
MedLine Citation:
PMID:  20655971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and fluoxetine (FLX) have additive effects in the treatment of major depressive disorder, and FLX up-regulates genes that regulate fatty acid biosynthesis in vitro. Although these data suggest that FLX may augment n-3 fatty acid biosynthesis, the in vivo effects of FLX treatment on PUFA biosynthesis and peripheral and central membrane compositions are not known. In the present study, male and female rats were treated with FLX (10 mg/kg/day) through their drinking water for 30 days (P60-P90). Plasma FLX and norfluoxetine (NFLX) concentrations were determined by liquid chromatography tandem mass spectrometry, and erythrocyte and prefrontal cortex (PFC) fatty acid composition determined by gas chromatography. To confirm central effects of FLX, serotonin turnover in the PFC was determined by high performance liquid chromatography. Chronic FLX treatment resulted in clinically-relevant plasma FLX concentrations in male and female rats, and significantly decreased serotonin turnover in the PFC. After correcting for multiple comparisons, chronic FLX treatment did not significantly alter erythrocyte fatty acid composition in male or female rats. Chronic FLX treatment significantly and selectively increased docosapentaenoic acid (22:5n-6) in the PFC of female rats, but not in male rats. These preclinical findings do not support the hypothesis that chronic FLX treatment increases n-3 fatty acid biosynthesis or membrane composition.
Authors:
Robert K McNamara; Jessica A Able; Therese Rider; Patrick Tso; Ronald Jandacek
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-23
Journal Detail:
Title:  Progress in neuro-psychopharmacology & biological psychiatry     Volume:  34     ISSN:  1878-4216     ISO Abbreviation:  Prog. Neuropsychopharmacol. Biol. Psychiatry     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-12-29     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  8211617     Medline TA:  Prog Neuropsychopharmacol Biol Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  1317-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. robert.mcnamara@uc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidepressive Agents, Second-Generation / pharmacology*
Body Weight / drug effects
Chromatography, Gas / methods
Chromatography, High Pressure Liquid / methods
Erythrocytes / drug effects*
Fatty Acids / metabolism*
Female
Fluoxetine / analogs & derivatives,  blood,  pharmacology*
Male
Prefrontal Cortex / drug effects*
Random Allocation
Rats
Rats, Long-Evans
Serotonin / metabolism
Grant Support
ID/Acronym/Agency:
DK59630/DK/NIDDK NIH HHS; MH073704/MH/NIMH NIH HHS; MH074858/MH/NIMH NIH HHS; R21 MH073704-02/MH/NIMH NIH HHS; R21 MH074858-02/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antidepressive Agents, Second-Generation; 0/Fatty Acids; 50-67-9/Serotonin; 54910-89-3/Fluoxetine; 56161-73-0/norfluoxetine
Comments/Corrections

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