Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus.
Lêda S B Garcia, Clarissa M Comim, Samira S Valvassori, Gislaine Z Réus, Luciana M Barbosa, Ana Cristina Andreazza, Laura Stertz, Gabriel R Fries, Elaine Cristina Gavioli, Flávio Kapczinski, João Quevedo
Progress in neuro-psychopharmacology & biological psychiatry January 1, 2008 DOI: 10.1016/j.pnpbp.2007.07.027 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ketamine Imipramine |
| Dose | Ketamine 5, 10, 15 mg/kg; imipramine 10, 20, 30 mg/kg |
| Duration | Acute administration |
| Measures | Forced swimming test, Open-field test, ELISA-sandwich assay |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine at 10 and 15 mg/kg and imipramine at 20 and 30 mg/kg reduced immobility time in the forced swimming test without affecting locomotion. Only ketamine at the higher dose increased hippocampal BDNF protein levels, suggesting this increase may be necessary for its rapid antidepressant action. |
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.