P.3.d.015 Treatment with memantine and imipramine induces changes in mitochondrial respiratory chain activity in the rat brain

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.

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Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2011.00543.x ◽

2011 ◽

Vol 23 (3) ◽

pp. 106-111 ◽

Cited By ~ 2

Author(s):

Tiago P. Freitas ◽

Gislaine T. Rezin ◽

Daiane B. Fraga ◽

Morgana Moretti ◽

Julia S. Vieira ◽

...

Keyword(s):

Animal Model ◽

Prefrontal Cortex ◽

Respiratory Chain ◽

Rebound Effect ◽

Mitochondrial Respiratory Chain ◽

Face Validity ◽

Mitochondrial Respiratory Chain Activity ◽

Respiratory Chain Activity ◽

The Brain ◽

Mitochondrial Respiratory

Objectives: Bipolar disorder (BD) is a mental illness associated with higher rates of suicide. The present study aims to investigate the brain mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Methods: Adult male Wistar rats received a single intracerebroventricular administration of ouabain (10−3 and 10−2 M) or vehicle. Locomotor activity was measured using the open field test. Mitochondrial respiratory chain activity was measured in the brain of rats 1 h and 7 days after ouabain administration.Results: Our results showed that spontaneous locomotion was increased 1 h and 7 days after ouabain administration. Complexes I, III and IV activities were increased in the prefrontal cortex, hippocampus and striatum immediately after the administration of ouabain, at the concentration of 10−3 and 10−2 M. Moreover, complex II activity was increased only in the prefrontal cortex at the concentration of 10−2 M. On the other hand, no significant alterations were observed in complex I activity 7 days after ouabain administration. However, an increase in complexes II, III and IV activities was observed only in the prefrontal cortex at the concentration of 10−2 M.Conclusion: Our findings suggest an increase in the activities of mitochondrial respiratory chain in this model of mania. A possible explanation is that these findings occur as a rebound effect trying to compensate for a decrease of ATP deprivation in BD. The present findings suggest that this model may present good face validity and a limitation in construct validity.

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