title: Behavioral changes and mitochondrial dysfunction in a rat model of schizophrenia induced by ketamine.
abstract: Evidence from the literature indicates that mitochondrial dysfunction occurs in schizophrenia and other psychiatric disorders. To produce an animal model that simulates psychotic symptoms analogous to those seen in schizophrenic patients, sub-anesthetic doses of N-methyl-D-aspartate (NMDA) receptor antagonists (such as ketamine) have been used. The aim of this study was to evaluate behavioral changes and mitochondrial dysfunction in rats administered ketamine for 7 consecutive days. Behavioral evaluation was performed using an activity monitor 1, 3 and 6 h after the last injection. The activities of mitochondrial respiratory chain complexes I, II, I-III and IV in multiple brain regions (prefrontal cortex, striatum and hippocampus) were also evaluated. Our results showed that hyperlocomotion occurred in the ketamine group 1 and 3 h after the last injection. Stereotypic movements were elevated only when animals were evaluated 1 h after receiving ketamine. In addition, we found that ketamine administration affects the respiratory chain, altering the activity of respiratory chain complexes in the striatum and hippocampus after 1 h, those in the prefrontal cortex and hippocampus after 3 h and those in the prefrontal cortex and striatum 6 h after the last administration of ketamine. These findings suggest that ketamine alters the behavior of rats and changes the activity of respiratory chain complexes in multiple brain regions at different time points.
authors.affiliation: Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: de Oliveira
authors.forename: Daiane B
authors.initials: DB
authors.lastname: Fraga
authors.forename: Renata D
authors.initials: RD
authors.lastname: De Luca
authors.forename: Leila
authors.initials: L
authors.lastname: Canever
authors.forename: Fernando V
authors.initials: FV
authors.lastname: Ghedim
authors.forename: Maria Paula P
authors.initials: MP
authors.lastname: Matos
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Zugno
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004579:Electron Transport / Q000187:drug effects*; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000503:physiopathology*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III