title: 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.
authors.affiliation: Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil. gislainezilli@hotmail.com
authors.forename: Gislaine Z
authors.initials: GZ
authors.lastname: Réus
authors.forename: Helena M
authors.initials: HM
authors.lastname: Abelaira
authors.forename: Fabiano R
authors.initials: FR
authors.lastname: Agostinho
authors.forename: Karine F
authors.initials: KF
authors.lastname: Ribeiro
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Vitto
authors.forename: Thais F
authors.initials: TF
authors.lastname: Luciano
authors.forename: Claúdio T de
authors.initials: CT
authors.lastname: Souza
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005473:Fluoxetine / Q000008:administration & dosage*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects*; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D001569:Benzodiazepines; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004338:Drug Combinations; D005473:Fluoxetine; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D017367:Selective Serotonin Reuptake Inhibitors; D051025:bcl-Associated Death Protein; C494821:Bad protein, rat; C492572:olanzapine-fluoxetine combination