title: Acute administration of ketamine reverses the inhibition of mitochondrial respiratory chain induced by chronic mild stress.
abstract: Modulation and dysfunction of the glutamatergic system seems to be involved in depression. Recently a renewed interest in the glutamatergic system as a treatment option for major depression emerged by the finding that the glutamate N-methyl-D-aspartate (NMDA) antagonist ketamine leads to a rapid improvement of depressive symptoms. Several works support the hypothesis that metabolism impairment is involved in the pathophysiology of depression. We have also recently reported that mitochondrial respiratory chain complexes I, III and IV were inhibited in cerebral cortex and cerebellum of rats after 40 days of chronic mild stress (CMS), which is used as an animal model of depression. Thus, we investigated whether the inhibition of these enzymes may be reversed by acute administration of ketamine (15 mg/kg). We verified that CMS decreased the intake of sweet food and ketamine was not able to reverse such effect. Adrenal gland weight was increased in stressed rats and ketamine reversed this alteration. Control group gained weight after 40 days but stressed group did not gain weight after the same period. Stressed animals gained weight after acute administration of ketamine, when compared to the body weight assessed at the beginning of the experiment. Finally, we verified that complexes I, III and IV were inhibited after CMS in cerebral cortex and cerebellum and acute administration of ketamine reversed this inhibition. Based on the present findings, we hypothesized that CMS induces inhibition of mitochondrial respiratory chain (complexes I, III and IV) and that acute administration of ketamine reverses such effect.
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Cinara L
authors.initials: CL
authors.lastname: Gonçalves
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Daufenbach
authors.forename: Daiane B
authors.initials: DB
authors.lastname: Fraga
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Santos
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.forename: Fernanda V
authors.initials: FV
authors.lastname: Hermani
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Comim
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004435:Eating / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III