Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1317-21. doi: 10.1016/j.pnpbp.2010.07.016. Epub 2010 Jul 23.
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.
ω-3（n-3）多不饱和脂肪酸（PUFA）和氟西汀（FLX）在治疗重度抑郁症方面具有协同作用，并且 FLX 可体外上调调节脂肪酸生物合成的基因。尽管这些数据表明 FLX 可能增强 n-3 脂肪酸的生物合成，但 FLX 治疗对 PUFA 生物合成以及外周和中枢膜组成的体内影响尚不清楚。在本研究中，雄性和雌性大鼠通过饮用水连续 30 天（P60-P90）接受 FLX（10mg/kg/天）治疗。通过液相色谱串联质谱法测定血浆中的 FLX 和去甲氟西汀（NFLX）浓度，通过气相色谱法测定红细胞和前额皮质（PFC）中的脂肪酸组成。为了证实 FLX 的中枢作用，通过高效液相色谱法测定 PFC 中的 5-羟色胺周转率。慢性 FLX 治疗导致雄性和雌性大鼠血浆中出现临床相关的 FLX 浓度，并显著降低 PFC 中的 5-羟色胺周转率。经多次比较校正后，慢性 FLX 治疗并未显著改变雄性或雌性大鼠的红细胞脂肪酸组成。慢性 FLX 治疗可显著选择性地增加雌性大鼠 PFC 中的二十二碳五烯酸（22:5n-6），但对雄性大鼠无此作用。这些临床前发现并不支持慢性 FLX 治疗增加 n-3 脂肪酸生物合成或膜组成的假设。
