Background
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) class used for antidepressant research.
Fluoxetine blocks the downregulation of cell proliferation resulting from inescapable shock (IS) of hippocampal cell[1]. Fluoxetine increases the number of newborn cells in the dentate gyrus of the hippocampus of adult rat. Fluoxetine also increases the number of proliferating cells in the prelimbic cortex[2]. Fluoxetine accelerates the maturation of immature neurons. Fluoxetine enhances neurogenesis-dependent long-term potentiation (LTP) in the dentate gyrus[3]. Fluoxetine, but not citalopram, fluvoxamine, paroxetine and sertraline, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Fluoxetine produces robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration[4].
Fluoxetine treatment also reverses the deficit in escape latency observed in animals exposed to inescapable shock in adult male Sprague-Dawley rats[1]. Fluoxetine (5 mg/kg) alone increases cell proliferation in the dentate gyrus. Coadministration (fluoxetine 5 mg/kg + olanzapine) also significantly increases the number of BrdU-positive cells compared with the control group[2]. Fluoxetine combined with Olanzapine produces robust, sustained increases of extracellular levels of dopamine ([DA](ex)) and norepinephrine ([NE](ex)) up to 361% and 272% of the baseline, respectively, which are significantly greater than either drug alone[5].
氟西汀是一种选择性 5-羟色胺再摄取抑制剂 (SSRI)，用于抗抑郁研究。
氟西汀阻断海马细胞不可避免的休克 (IS) 引起的细胞增殖下调[1]。 Fluoxetine 增加成年大鼠海马齿状回新生细胞的数量。氟西汀还增加了前边缘皮质中增殖细胞的数量 [2]。氟西汀加速未成熟神经元的成熟。氟西汀增强齿状回神经发生依赖性长时程增强 (LTP) [3]。氟西汀，而不是西酞普兰、氟伏沙明、帕罗西汀和舍曲林，增加前额皮质中去甲肾上腺素和多巴胺的细胞外水平。急性全身给药后，氟西汀使去甲肾上腺素和多巴胺的细胞外浓度显着持续增加[4]。
氟西汀治疗还可以逆转成年雄性 Sprague-Dawley 暴露于不可避免休克的动物中观察到的逃避潜伏期缺陷大鼠[1]。 Fluoxetine (5 mg/kg) 单独增加齿状回的细胞增殖。与对照组相比，共同给药（氟西汀 5 mg/kg + 奥氮平）也显着增加了 BrdU 阳性细胞的数量 [2]。氟西汀联合奥氮平可使细胞外多巴胺 ([DA](ex)) 和去甲肾上腺素 ([NE](ex)) 水平显着持续增加，分别达到基线的 361% 和 272%，显着高于基线水平单独使用任何一种药物[5]。
[1]. Malberg JE, et al. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003 Sep;28(9):1562-71 [2]. Kodama M, et al. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry. 2004 Oct 15;56(8):570-80. [3]. Wang JW, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci. 2008 Feb 6;28(6):1374-84. [4]. Bymaster FP, et al. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl). 2002 Apr;160(4):353-61 [5]. Zhang W, et al. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology. 2000 Sep;23(3):250-62. [6]. Avitsur R1. Increased symptoms of illness following prenatal stress: Can it be prevented by fluoxetine? Behav Brain Res. 2017 Jan 15;317:62-70.
Protocol
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Animal experiment:
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Male Sprague-Dawley rats weighing 250-300 g are housed under a 12-hour light/12-hour dark cycle (lights on at 7:00?am, lights off at 7:00?pm) and at constant temperature (25°C) and humidity and allowed free access to food and water. For chronic drug treatments, rats are administered fluoxetine (5 mg/kg/day) or saline by intraperitoneal (IP) injection once daily and olanzapine or vehicle in the drinking water for 21 days (vehicle-treated control, fluoxetine, and olanzapine alone) plus the combination of fluoxetine and olanzapine. For combination treatment, olanzapine is chosen because fluoxetine is known to interfere with the metabolism of olanzapine and raise the blood levels by up to 4-6 times. Olanzapine is dissolved in hydrochloric acid (HCl), then adjusted back to pH 6 with 1 N sodium hydroxide to make the stock solution of 3 mg/mL concentration. The same amount of vehicle solution is added to the water for the control animals. Fluid intake is measured three times per week, and drinking bottles are replenwashed with fresh drug solution. There are no differences in fluid intake among the treatment groups. For subchronic treatment, drugs are administered exactly the same way but for a total period of 7 days.
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参考文献:
[1]. Malberg JE, et al. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003 Sep;28(9):1562-71
[2]. Avitsur R1. Increased symptoms of illness following prenatal stress: Can it be prevented by fluoxetine Behav Brain Res. 2017 Jan 15;317:62-70.
[3]. Kodama M, et al. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry. 2004 Oct 15;56(8):570-80.
[4]. Wang JW, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci. 2008 Feb 6;28(6):1374-84.
[5]. Bymaster FP, et al. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl). 2002 Apr;160(4):353-61
[6]. Zhang W, et al. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology. 2000 Sep;23(3):250-62.
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