The role of ketamine in major depressive disorders: Effects on parvalbumin-positive interneurons in hippocampus

Exp Biol Med (Maywood). 2023 Apr;248(7):588-595. doi: 10.1177/15353702231170007. Epub 2023 May 9.


Major depressive disorder (MDD) is a complex illness that is arising as a growing public health concern. Although several brain areas are related to this type of disorders, at the cellular level, the parvalbumin-positive cells of the hippocampus interplay a very relevant role. They control pyramidal cell bursts, neuronal networks, basic microcircuit functions, and other complex neuronal tasks involved in mood disorders. In resistant depressions, the efficacy of current antidepressant treatments drops dramatically, so the new rapid-acting antidepressants (RAADs) are being postulated as novel treatments. Ketamine at subanesthetic doses and its derivative metabolites have been proposed as RAADs due to their rapid and sustained action by blocking N-methyl-d-aspartate (NMDA) receptors, which in turn lead to the release of brain-derived neurotrophic factor (BDNF). This mechanism produces a rapid plasticity activation mediated by neurotransmitter homeostasis, synapse recovery, and increased dendritic spines and therefore, it is a promising therapeutic approach to improve cognitive symptoms in MDD.

Keywords: N-methyl-d-aspartate receptors (NMDARs); brain-derived neurotrophic factor (BDNF); hippocampus (HC); interneurons (INs); ketamine; major depressive disorder (MDD).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / metabolism
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Brain-Derived Neurotrophic Factor / metabolism
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / metabolism
  • Hippocampus / metabolism
  • Humans
  • Interneurons / metabolism
  • Ketamine* / pharmacology
  • Parvalbumins / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, N-Methyl-D-Aspartate / therapeutic use


  • Ketamine
  • Parvalbumins
  • Receptors, N-Methyl-D-Aspartate
  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor