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The influence of aripiprazole, olanzapine and enriched environment on depressant-like behavior, spatial memory dysfunction and hippocampal level of BDNF in prenatally stressed rats

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Abstract

Background

Cognitive function deficits caused by impaired neurogenesis of the brain structures are considered an important pathogenic factor in many neurological and mental diseases such as schizophrenia and depression.

The aim of the study was to determine the effect of the enriched environment on cognitive functions and antidepressant-like effect of prenatally stressed rats. It was important to determine the effect of aripiprazole ARI and olanzapine OLA and clarify whether the enriched environment induces increases in brain derived neurothropic factor BDNF in the hippocampus in the prenatally stressed group (PSG) and non-stressed control group (NSCG).

Methods

The effect of chronic stress applied to pregnant rats and the use of ARI (1.5 mg/kg ip) and OLA (0.5 mg/kg ip) were studied in the Morris water maze (MWM), Porsolt Forced swimming test (FST) and by determining BDNF levels.

Results

The results indicated that enriched environment improved spatial memory and also had an antidepressant-like effect on prenatally stressed rats. ARI improved spatial memory both in the NSCG and PSG, while OLA caused memory improvement only in the PSG. Moreover, both ARI and OLA reduced immobility time in the NSCG and PSG.

In PSG rats, BDNF decrease was observed while chronic treatment with ARI and OLA increased BDNF levels in the hippocampi of NSCG and PSG rats.

Conclusion

It has been confirmed that enriched environment improves spatial memory of animals, removes symptoms of stress, has an antidepressant-like effect, and that new neuroleptics, such as ARI or OLA, modulate these functions (increased BDNF).

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Abbreviations

AMPA:

2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid

ARI:

aripiprazole

BDNF:

brain derived neurotrophic factor

CMC:

carboxymethylcellulose sodium

CNS:

central nervous system

D2, D3, D4:

dopamine receptors

FST:

forced swimming test

HPA:

hypothalamic-pituitary-adrenal axis

ip :

intraperitoneally

MWM:

Morris water maze

NSCG:

non-stresseded control group

OLA:

olanzapine

PSG:

prenatally stressed group

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Authors and Affiliations

  1. Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Poznań, Poland

    Elżbieta Nowakowska, Krzysztof Kus & Piotr Ratajczak

  2. Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland

    Michał Cichocki

  3. Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland

    Anna Woźniak

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  1. Elżbieta Nowakowska
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  2. Krzysztof Kus
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  3. Piotr Ratajczak
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Correspondence to Elżbieta Nowakowska.

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Nowakowska, E., Kus, K., Ratajczak, P. et al. The influence of aripiprazole, olanzapine and enriched environment on depressant-like behavior, spatial memory dysfunction and hippocampal level of BDNF in prenatally stressed rats. Pharmacol. Rep 66, 404–411 (2014). https://doi.org/10.1016/j.pharep.2013.12.008

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  • DOI: https://doi.org/10.1016/j.pharep.2013.12.008

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