title: Acute and Chronic Treatments with Quetiapine Increase Mitochondrial Respiratory Chain Complex Activity in the Rat Brain.
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.
authors.forename: Zuleide M
authors.initials: ZM
authors.lastname: Ignácio
authors.affiliation: Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX 77054, USA. gislaine.z.reus@uth.tmc.edu.
authors.forename: Gislaine Z
authors.initials: GZ
authors.lastname: Réus
authors.forename: Helena M
authors.initials: HM
authors.lastname: Abelaira
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Titus
authors.forename: Anelise S
authors.initials: AS
authors.lastname: Carlessi
authors.forename: Jaine R
authors.initials: JR
authors.lastname: da Luz
authors.forename: Beatriz I
authors.initials: BI
authors.lastname: Matias
authors.forename: Livia
authors.initials: L
authors.lastname: Bruchchen
authors.forename: Milena
authors.initials: M
authors.lastname: Carvalho-Silva
authors.forename: Lara M
authors.initials: LM
authors.lastname: Gomes
authors.forename: Joyce
authors.initials: J
authors.lastname: Rebelo
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009097:Multienzyme Complexes / Q000145:classification / Q000378:metabolism*; D000069348:Quetiapine Fumarate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D009097:Multienzyme Complexes; D000069348:Quetiapine Fumarate; D003402:Creatine Kinase; D007099:Imipramine