Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes
G.S.B. Viana, E.M. Do Vale, Ana Giullia de Alencar Araújo, N. C. Coêlho, S. M. Andrade, R. O. Costa, P. Aquino, C. Sousa, I.S. de Medeiros, S. Vasconcelos, K.R.T. Neves
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas December 18, 2020 DOI: 10.1590/1414-431x202010107 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Male Swiss mice |
| Interventions | Ketamine Imipramine |
| Dose | 2, 5, or 10 mg/kg |
| Duration | 30-minute, 15-day, and 30-day time points after single administration |
| Topics | Esketamine Ketamine |
| Post-publication review | 2 comments on PubPeer (opens in new tab) · last active May 2021 |
| Key findings | A single oral dose of ketamine (5 or 10 mg/kg) produced rapid and long-lasting antidepressant-like effects in mice, associated with decreased GSK-3 and HDAC immunoreactivity and increased BDNF and GFAP expression in brain regions up to 30 days later. |
Abstract
Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug’s sustained antidepressant-like effects.