title: The effects of tianeptine, olanzapine and fluoxetine on the cognitive behaviors of unpredictable chronic mild stress-exposed mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Gumuslu
authors.forename: O
authors.initials: O
authors.lastname: Mutlu
authors.forename: D
authors.initials: D
authors.lastname: Sunnetci
authors.forename: G
authors.initials: G
authors.lastname: Ulak
authors.forename: I K
authors.initials: IK
authors.lastname: Celikyurt
authors.forename: N
authors.initials: N
authors.lastname: Cine
authors.forename: F
authors.initials: F
authors.lastname: Akar
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D003071:Cognition / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013315:Stress, Psychological / Q000523:psychology*; D013841:Thiazepines / Q000494:pharmacology*
chemical_list: D001569:Benzodiazepines; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D005473:Fluoxetine; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors; D013841:Thiazepines; C492004:Creb1 protein, mouse; C050504:tianeptine