Olanzapine plus fluoxetine treatment increases Nt-3 protein levels in the rat prefrontal cortex

Abstract

Evidence is emerging for a role for neurotrophins in the treatment of mood disorders. In this study, we evaluated the effects of chronic administration of fluoxetine, olanzapine and the combination of fluoxetine/olanzapine on the brain-derived-neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in the rat brain. Wistar rats received daily injections of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg) for 28 days, and we evaluated for BDNF, NGF and NT-3 protein levels in the prefrontal cortex, hippocampus and amygdala. Our results showed that treatment with fluoxetine and olanzapine alone or in combination did not alter BDNF in the prefrontal cortex (p=0.37), hippocampus (p=0.98) and amygdala (p=0.57) or NGF protein levels in the prefrontal cortex (p=0.72), hippocampus (p=0.23) and amygdala (p=0.64), but NT-3 protein levels were increased by olanzapine 6 mg/kg/fluoxetine 25mg/kg combination in the prefrontal cortex (p=0.03), in the hippocampus (p=0.83) and amygdala (p=0.88) NT-3 protein levels did not alter. Finally, these findings further support the hypothesis that NT-3 could be involved in the effect of treatment with antipsychotic and antidepressant combination in mood disorders.