Effect of chronic fluoxetine treatment on male and female rat erythrocyte and prefrontal cortex fatty acid composition

Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and fluoxetine (FIX) have additive effects in the treatment of major depressive disorder, and FIX up-regulates genes that regulate fatty acid biosynthesis in vitro Although these data suggest that FIX may augment n-3 fatty acid biosynthesis, the in vivo effects of FIX treatment on PUFA biosynthesis and peripheral and central membrane compositions are not known. In the present study, male and female rats were treated with FIX (10 mg/kg/day) through their drinking water for 30 days (P60-P90) Plasma FIX and norfluoxetine (NFLX) concentrations were determined by liquid chromatography tandem mass spectrometry, and erythrocyte and prefiontal cortex (PFC) fatty acid composition determined by gas chromatography To confirm central effects of FIX, serotonin turnover in the PFC was determined by high performance liquid chromatography Chronic FIX treatment resulted in clinically-relevant plasma FIX concentrations in male and female rats. and significantly decreased serotonin turnover in the PFC After correcting for multiple comparisons. chronic FIX treatment did not significantly alter erythrocyte fatty acid composition in male or female rats Chronic FIX 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 FIX treatment increases n-3 fatty acid biosynthesis or membrane composition (C) 2010 Elsevier Inc All rights reserved.