Olanzapine plus fluoxetine treatment alters mitochondrial respiratory chain activity in the rat brain

Abstract

Agostinho FR, Réus GZ, Stringari RB, Ribeiro KF, Ferreira GK, Jeremias IC, Scaini G, Rezin GT, Streck EL, Quevedo J. Olanzapine plus fluoxetine treatment alters mitochondrial respiratory chain activity in the rat brain.Background:Evidence is emerging for the role of dysfunctional mitochondria in pathophysiology and treatment of mood disorders. In this study, we evaluated the effects of acute and chronic administration of fluoxetine (FLX), olanzapine (OLZ) and the combination of FLX/OLZ on mitochondrial respiratory chain activity in the rat brain.Methods:For acute treatment, Wistar rats received one single injection of OLZ (3 or 6 mg/kg) and/or FLX (12 or 25 mg/kg) and for chronic treatment, rats received daily injections of OLZ (3 or 6 mg/kg) and/or FLX (12 or 25 mg/kg) for 28 days and we evaluated the activity of mitochondrial respiratory chain complexes I, II, II–III and IV in prefrontal cortex, hippocampus and striatum.Results:Our results showed that both acute and chronic treatments with FLX and OLZ alone or in combination altered respiratory chain complexes activity in the rat brain, but in combination we observed larger alterations.Conclusions:Finally, these findings further support the hypothesis that metabolism energy could be involved in the treatment with antipsychotics and antidepressants in combination to mood disorders.