Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus.
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.
Garcia
Lêda S B
LS
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.
Comim
Clarissa M
CM
Valvassori
Samira S
SS
Réus
Gislaine Z
GZ
Barbosa
Luciana M
LM
Andreazza
Ana Cristina
AC
Stertz
Laura
L
Fries
Gabriel R
GR
Gavioli
Elaine Cristina
EC
Kapczinski
Flavio
F
Quevedo
João
J
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D007649:Ketamine; D007099:Imipramine