Ketamine: Synaptogenesis, immunomodulation and glycogen synthase kinase-3 as underlying mechanisms of its antidepressant properties

P. A. Zunszain, M. A. Horowitz, A. Cattaneo, M. M. Lupi, C. M. Pariante

Research output: Contribution to journalArticlepeer-review

Abstract

Major depressive disorder is an extremely debilitating condition affecting millions of people worldwide. Nevertheless, currently available antidepressant medications still have important limitations, such as a low response rate and a time lag for treatment response that represent a significant problem when dealing with individuals who are vulnerable and prone to self-harm. Recent clinical trials have shown that the N-methyl-D-aspartate receptor antagonist, ketamine, can induce an antidepressant response within hours, which lasts up to 2 weeks, and is effective even in treatment-resistant patients. Nonetheless, its use is limited due to its psychotomimetic and addictive properties. Understanding the molecular pathways through which ketamine exerts its antidepressant effects would help in the developing of novel antidepressant agents that do not evoke the same negative side effects of this drug. This review focuses specifically on the effects of ketamine on three molecular mechanisms that are relevant to depression: synaptogenesis, immunomodulation and regulation of glycogen synthase kinase-3 activity.

Original languageEnglish
Pages (from-to)1236-1241
Number of pages6
JournalMolecular Psychiatry
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • BDNF
  • circadian
  • depression
  • glutamatergic
  • inflammation
  • NMDA

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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