The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain

Journal of Psychiatric Research
Gislaine Z RéusJoão Quevedo

Abstract

Recently, several studies have emerged suggesting a role of the intracellular survival pathways in the treatment of mood disorders. In addition, the beneficial effects of using a combination of antipsychotics and antidepressants have been shown. With this in mind, we evaluated the effects of the acute administration of fluoxetine (FLX), olanzapine (OLZ) and the combination of fluoxetine/olanzapine on the brain-derived-neurotrophic factor (BDNF), cAMP response element-binding (CREB), Protein Kinase B (PKB, Akt), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated death promoter (BAD) in the rat brain. Adult Wistar rats received an acute injection of OLZ (3 or 6 mg/kg) and/or FLX (12.5 or 25 mg/kg), and were evaluated for Akt, BDNF, CREB, Bcl-2 and BAD protein levels in the prefrontal cortex, hippocampus and striatum. Our results showed that treatment with FLX and OLZ alone or in combination increased the Akt, CREB, BDNF, Bcl-2 and BAD levels in the prefrontal cortex, hippocampus and striatum. However, the combination of FLX and OLZ at high doses was associated with a greater increase in the levels of Akt in the prefrontal cortex, and did not have an effect on the levels of BAD in any of the brain areas that we evaluated. Finally, the...Continue Reading

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Citations

Feb 15, 2014·Advances in Pharmacological Sciences·Azam BakhtiarianVahid Nikoui
Dec 3, 2014·European Journal of Pharmacology·Barbara J CaldaroneSarah L King
Sep 6, 2014·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Myoung Suk SeoBrian Dean
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Apr 15, 2017·Behavioural Brain Research·Isabel Vieira de Assis LimaAntônio Carlos Pinheiro de Oliveira
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Jan 29, 2019·Early Intervention in Psychiatry·Oliver D RobertsonSeetal Dodd
Jan 6, 2021·International Journal of Molecular Sciences·Motohiro OkadaTakashi Shiroyama

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