Department of Psychobiology, University of Valencia, Valencia, Spain.
Behav Brain Res. 2010 Dec 25;214(2):343-8. doi: 10.1016/j.bbr.2010.06.002. Epub 2010 Jun 9.
We have previously observed that, while the impairing effects of amitriptyline on inhibitory avoidance in mice are consistently observed, those of acute fluoxetine are negligible. Two experiments were designed to investigate whether a regular dose of fluoxetine potentiates the effect of a low dose of amitriptyline that is ineffective when administered alone. Male and female CD1 mice were administered i.p. 30 min before training, as follows. In the first experiment, they were injected with saline, one of three doses of amitriptyline (2.5, 5, 10mg/kg), one dose of fluoxetine (15 mg/kg), or a combination of amitriptyline (2.5mg/kg) and fluoxetine (15 mg/kg). In the second experiment, the mice were injected with saline, amitriptyline (2.5mg/kg), one of three doses of fluoxetine (10, 15, 20mg/kg), or a combination of 2.5mg/kg of amitriptyline and one of the three mentioned doses of fluoxetine. Drug doses were selected based on previous experiments in our laboratory reported in other publications. The behavioural procedure used to test the effects of these treatments was step-through inhibitory avoidance. The joint administration of amitriptyline 2.5mg/kg and fluoxetine 15 mg/kg had a clear impairing effect on inhibitory avoidance as observed in the two experiments. The dose of 2.5mg/kg of amitriptyline, given alone, was ineffective. Doses of 5mg/kg, or higher, of amitriptyline impaired inhibitory avoidance. The only effect detected when fluoxetine was administered separately was in the males of the experiment 1, which exhibited less avoidance than controls. Our preclinical research throws light on the benefits of the combined administration of antidepressants.
我们之前曾观察到，虽然阿米替林对小鼠抑制性回避的损害作用始终存在，但氟西汀的急性作用却可以忽略不计。设计了两项实验来研究，当单独给予时无效的低剂量阿米替林是否可以增强常规剂量氟西汀的作用。雄性和雌性 CD1 小鼠在训练前 30 分钟通过腹腔注射给予以下药物。在第一个实验中，它们被注射生理盐水，三种剂量的阿米替林（2.5、5、10mg/kg）之一，一种剂量的氟西汀（15mg/kg），或阿米替林（2.5mg/kg）和氟西汀（15mg/kg）的组合。在第二个实验中，将盐水、阿米替林（2.5mg/kg）、三种剂量的氟西汀（10、15、20mg/kg）之一或 2.5mg/kg 的阿米替林和三种剂量的氟西汀之一的组合注射到小鼠体内。药物剂量是根据我们实验室之前在其他出版物中报道的实验选择的。用于测试这些治疗效果的行为程序是步出抑制性回避。如在两个实验中观察到的，联合给予阿米替林 2.5mg/kg 和氟西汀 15mg/kg 对抑制性回避有明显的损害作用。单独给予 2.5mg/kg 的阿米替林剂量无效。5mg/kg 或更高剂量的阿米替林损害了抑制性回避。当单独给予氟西汀时，仅在实验 1 的雄性中检测到效果，其回避行为比对照组少。我们的临床前研究揭示了联合使用抗抑郁药的益处。
