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

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, these findings further support the hypothesis that treatment with FLX and OLZ alone or in combination exert neuroprotective effects, and that intracellular survival pathways could be involved in the therapeutic effects of combining antipsychotic and antidepressant drugs in mood disorders.

journal_name

J Psychiatr Res

journal_title

Journal of psychiatric research

authors

Réus GZ,Abelaira HM,Agostinho FR,Ribeiro KF,Vitto MF,Luciano TF,Souza CT,Quevedo J

doi

10.1016/j.jpsychires.2012.04.016

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

1029-35

issue

8

eissn

0022-3956

issn

1879-1379

pii

S0022-3956(12)00130-6

journal_volume

46

pub_type

杂志文章

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