Drug Res (Stuttg) 2013; 63(10): 532-539
DOI: 10.1055/s-0033-1347237
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

The Effects of Tianeptine, Olanzapine and Fluoxetine on the Cognitive Behaviors of Unpredictable Chronic Mild Stress-exposed Mice

E. Gumuslu
1   Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
O. Mutlu
2   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
D. Sunnetci
1   Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
G. Ulak
2   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
I. K. Celikyurt
2   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
N. Cine
1   Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
F. Akar
2   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
› Author Affiliations
Further Information

Publication History

received 27 February 2013

accepted 09 May 2013

Publication Date:
18 June 2013 (online)

Preview

Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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.