Gumuslu E, Mutlu O, Sunnetci D, Ulak G, Celikyurt I K, Cine N, Akar F
Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, Turkey.
Drug Res (Stuttg). 2013 Oct;63(10):532-9. doi: 10.1055/s-0033-1347237. Epub 2013 Jun 18.
Strong evidence indicates that impaired cognition is a core element of depression, and antidepressant treatment may ameliorate cognitive impairments experienced by depressive patients. Present study was performed to investigate effects of chronic tianeptine (5 mg/kg) or olanzapine (2.5 mg/kg) administration on cognitive behaviors of unpredictable chronic mild stress (UCMS)-exposed mice and to compare these effects to those induced by widely used SSRI antidepressant fluoxetine (15 mg/kg) in mice.
To investigate effects of these drugs, the Morris water maze test (MWM), elevated plus maze test (EPM) and radial arm maze test (RAM) were used. The effects of stress and drugs on gene expression in the hippocampus was determined by quantitative Real Time-PCR.
In MWM test, fluoxetine significantly increased escape latency of non-stressed mice in acquisition sessions and decreased time spent in escape platform quadrant in probe trial; tianeptine and olanzapine decreased enhancement in escape latency, and only olanzapine significantly enhanced attenuation in time spent in the escape platform quadrant in UCMS-exposed mice. In EPM test, all drugs significantly decreased enhancement in transfer latency in UCMS-exposed mice. In RAM test, fluoxetine significantly increased number of errors made by both non-stressed and UCMS-exposed mice.
Quantitative real-time PCR revealed that CREB and BDNF gene expression levels were significantly decreased in UCMS-exposed group, and this effect was significantly reversed by each of drugs tested. Our results seem to be test dependent and should be further investigated using different learning and memory tasks.
有力证据表明，认知功能受损是抑郁症的核心要素，抗抑郁治疗可能改善抑郁症患者所经历的认知障碍。本研究旨在探讨长期给予噻奈普汀（5毫克/千克）或奥氮平（2.5毫克/千克）对不可预测慢性轻度应激（UCMS）小鼠认知行为的影响，并将这些影响与广泛使用的SSRI类抗抑郁药氟西汀（15毫克/千克）对小鼠的影响进行比较。
为研究这些药物的作用，采用了莫里斯水迷宫试验（MWM）、高架十字迷宫试验（EPM）和放射状臂迷宫试验（RAM）。通过定量实时聚合酶链反应确定应激和药物对海马体基因表达的影响。
在MWM试验中，氟西汀显著增加了非应激小鼠在训练阶段的逃避潜伏期，并在探针试验中减少了在逃避平台象限的停留时间；噻奈普汀和奥氮平减少了逃避潜伏期的增加，并且只有奥氮平显著增强了UCMS小鼠在逃避平台象限停留时间的减少。在EPM试验中，所有药物均显著减少了UCMS小鼠转移潜伏期的增加。在RAM试验中，氟西汀显著增加了非应激和UCMS小鼠的错误次数。
定量实时聚合酶链反应显示，UCMS组中CREB和BDNF基因表达水平显著降低，而所测试的每种药物均显著逆转了这种效应。我们的结果似乎依赖于测试，应使用不同的学习和记忆任务进行进一步研究。
