Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Portugal.
Eur J Pharmacol. 2012 Nov 15;695(1-3):71-5. doi: 10.1016/j.ejphar.2012.08.020. Epub 2012 Sep 7.
Maternal separation (MS) induces depressive-like behavior and long-term changes in cognition in rats. Escitalopram is an antidepressant drug shown to reverse the depressive-like features caused by this stress model. However, it is not known if it can ameliorate the affected cognition. We now characterized the effect of escitalopram on hippocampal-dependent memory in rats submitted to the MS protocol. Male Wistar rats were assigned either to control (CTR) or maternal separated (MS) group. MS were separated from their dams between 2-14 postnatal days (PND) for 180min daily. Escitalopram was given in food pellets (0.34g/kg/day first 2 weeks and 0.41g/kg/day the subsequent period, average dose 25mg/kg) from PND 43 onwards, during 1 month. Depressive behavior was assessed in the forced swimming test (FST), and memory performance in the Morris water maze (MWM). Escitalopram significantly improved the FST's latency to despair in the MS group (n=6), but did not change the immobility time. All groups showed a significant learning effect in the MWM over time, but no differences have been found upon treatment (n=6). However, escitalopram treatment significantly increased the time spent on the platform quadrant in the probe trial in the MS group. We report here that chronic treatment with escitalopram is able to improve hippocampal dependent memory in a chronic stress model, while not changing the learning ability. Moreover, this is accompanied by an amelioration of the depressive like behavior. These results support the use of escitalopram to tackle underlying cognitive deficits caused by stress in early-life.
母体分离(MS)会在大鼠中诱导出抑郁样行为和认知的长期变化。艾司西酞普兰是一种抗抑郁药,已被证明可以逆转这种应激模型引起的抑郁样特征。然而,目前尚不清楚它是否能改善受影响的认知。我们现在描述了艾司西酞普兰对接受 MS 方案的大鼠海马依赖性记忆的影响。雄性 Wistar 大鼠被分配到对照组(CTRL)或母体分离(MS)组。MS 在出生后 2-14 天(PND)期间每天与它们的母鼠分离 180 分钟。艾司西酞普兰从 PND43 开始以食物丸的形式给药(前 2 周每天 0.34g/kg,随后的时间段每天 0.41g/kg,平均剂量 25mg/kg),持续 1 个月。在强迫游泳试验(FST)中评估抑郁行为,在 Morris 水迷宫(MWM)中评估记忆表现。艾司西酞普兰显著改善了 MS 组 FST 的绝望潜伏期(n=6),但没有改变不动时间。所有组在 MWM 中均表现出随时间的学习效应,但在治疗后没有发现差异(n=6)。然而,艾司西酞普兰治疗显著增加了 MS 组在探针试验中平台象限的停留时间。我们在这里报告,慢性艾司西酞普兰治疗能够改善慢性应激模型中的海马依赖性记忆,而不改变学习能力。此外,这伴随着抑郁样行为的改善。这些结果支持使用艾司西酞普兰来解决早期生活应激引起的潜在认知缺陷。