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Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus
Authors:Garcia Lêda S B  Comim Clarissa M  Valvassori Samira S  Réus Gislaine Z  Barbosa Luciana M  Andreazza Ana Cristina  Stertz Laura  Fries Gabriel R  Gavioli Elaine Cristina  Kapczinski Flavio  Quevedo João
Institution:1. Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil;2. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Bipolar Disorders Program, Centro de Pesquisas, Hospital de Clínicas. Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
Abstract:Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor. Clinical findings point to a rapid onset of action for ketamine on the treatment of major depression. Considering that classic antidepressants may take long-lasting time to exhibit their main therapeutic effects, the present study aims to compare the behavioral effects and the BDNF hippocampus levels of acute administration of ketamine and imipramine in rats. To this aim, rats were acutely treated with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and animal behavioral was assessed in the forced swimming and open-field tests. Afterwards, BDNF protein hippocampal levels were assessed in imipramine- and ketamine-treated rats by ELISA-sandwich assay. We observed that ketamine at the doses of 10 and 15 mg/kg, and imipramine at 20 and 30 mg/kg reduced immobility time compared to saline group, without affecting locomotor activity. Interesting enough, acute administration of ketamine at the higher dose, but not imipramine, increased BDNF protein levels in the rat hippocampus. In conclusion, our findings suggest that the increase of hippocampal BDNF protein levels induced by ketamine might be necessary to produce a rapid onset of antidepressant action.
Keywords:BDNF  brain-derived-neurotrophic factor  IP  intraperitoneal  EGTA  ethylene glycol tetraacetic acid  IMI  imipramine  KET  ketamine  NMDA  N-methyl-d-aspartate  OD  optical density  PMSF  phenylmethylsulfonyl fluoride  PBS  phosphate buffer solution  
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