Felbamate produces antidepressant-like actions in the chronic unpredictable mild stress and chronic social defeat stress models of depression

Fundam Clin Pharmacol. 2019 Dec;33(6):621-633. doi: 10.1111/fcp.12466. Epub 2019 Apr 24.

Abstract

Felbamate is an anticonvulsant used in the treatment of epilepsy. In this study, we investigated the antidepressant-like actions of felbamate in mice. The effects of felbamate were first assessed using the forced swimming test (FST) and tail suspension test (TST), and then investigated in the chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling cascade after chronic stress and felbamate treatment were also examined. It was found that felbamate exhibited antidepressant-like activities in the FST and TST without affecting the locomotor activity of mice. Felbamate was also effective in both the CUMS and CSDS models of depression. Moreover, felbamate administration fully restored the decreased hippocampal BDNF signaling pathway in both the CUMS-stressed and CSDS-stressed mice. Collectively, felbamate has antidepressant-like actions in mice involving the hippocampal BDNF system.

Keywords: brain-derived neurotrophic factor; chronic social defeat stress; chronic unpredictable mild stress; depression; felbamate.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Brain-Derived Neurotrophic Factor / physiology
  • Depression / drug therapy*
  • Disease Models, Animal
  • Felbamate / pharmacology*
  • Hindlimb Suspension
  • Hippocampus / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Stress, Psychological / drug therapy

Substances

  • Antidepressive Agents
  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Receptors, N-Methyl-D-Aspartate
  • Felbamate