Title:Acute and Chronic Treatments with Quetiapine Increase Mitochondrial Respiratory Chain Complex Activity in the Rat Brain
Volume: 12
Issue: 3
Author(s): Zuleide M. Ignacio, Gislaine Z. Reus, Helena M. Abelaira, Stephanie E. Titus, Anelise S. Carlessi, Jaine R. da Luz, Beatriz I. Matias, Livia Bruchchen, Milena Carvalho-Silva, Lara M. Gomes, Joyce Rebelo, Emilio L. Streck and Joao Quevedo
Affiliation:
Keywords:
Quetiapine; antidepressant, energy metabolism, creatine kinase, mitochondrial respiratory chain, depression.
Abstract: Several studies have found that the molecular mechanisms of mitochondrial energy metabolism are impaired in
major depressive disorder (MDD). Classic antidepressants and atypical antipsychotics can alter the function of enzymes
involved in adenosine triphosphate (ATP) metabolism. Quetiapine is an atypical antipsychotic that, in addition to having a
therapeutic benefit in treating MDD, appears to exert antioxidant and neuroprotective effects. Therefore, we aimed to
evaluate the acute and chronic effects of quetiapine on the activity of enzyme complexes I to IV of the mitochondrial respiratory
chain and creatine kinase (CK) in brain regions involved with MDD. After a single dose or serial injections over
14 days of quetiapine (20, 40, and 80 mg) were administered, isolates from the pre- frontal cortex, hippocampus,
amygdala and nucleus accumbens were analyzed for enzyme activity levels. The enzyme activity varied according to the
dose, brain region, and acute or chronic dosing protocols. In general, complexes I-III activity was increased, especially after
acute administration. Acute administration also increased the activity of complex IV and CK in the amygdala while
complex I was inhibited in the prefrontal cortex and nucleus accumbens. These results suggest that quetiapine produces an
increase in respiratory chain complex activity, which may be underlying its efficacy against psychiatric disorders and neuronal
damage.