A Review of the Mechanism of Antagonism of N-methyl-D-aspartate Receptor by Ketamine in Treatment-resistant Depression

Summary & key facts

This review explains how ketamine, a drug that blocks NMDA receptors, might work for people with treatment‑resistant depression. It says one injection of ketamine can rapidly reduce depressive symptoms, including acute suicidal behavior. The paper describes steps that could explain this: ketamine may raise glutamate, trigger growth of neuron branches, raise BDNF (a growth protein), and activate the mTOR growth pathway. These changes may help form new synapses and strengthen brain connections, which could improve symptoms. The authors present these ideas as proposed mechanisms rather than proven facts.

Key facts:

• The NMDA receptor (a brain receptor) is described as having a major role in the neurophysiology of depression.
• Ketamine is a prototypical NMDA antagonist and can work rapidly to control depressive symptoms, including acutely suicidal behavior, after a single injection.
• Ketamine may rapidly increase glutamate levels in the brain.
• Ketamine may lead to structural neuronal changes such as increased dendritic growth (growth of neuron branches).
• Increased dendritic growth may contribute to synaptogenesis, meaning the formation of new synapses (connections between neurons).
• Increased levels of brain-derived neurotrophic factor (BDNF), a protein that supports neuron growth, are reported as part of the proposed chain of effects after ketamine.
• Activation of the mTOR pathway (mechanistic target of rapamycin) together with increased BDNF may increase long-term potentiation (strengthening of neuron connections) and could result in improvement in depression symptoms.

Abstract

The biochemical processes involved in depression go beyond serotonin, norepinephrine, and dopamine. The N-methyl-D-aspartate (NMDA) receptor has a major role in the neurophysiology of depression. Ketamine, one of the prototypical NMDA antagonists, ...

Topics

Neurotransmitter Receptor Influence on Behavior Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Antidepressant Brain-derived neurotrophic factor Depression (economics) Dopamine Economics Epistemology Glutamate receptor Hippocampus Internal medicine Ketamine Long-term potentiation Macroeconomics Mechanism (biology) Medicine Neuroscience Neurotrophic factors NMDA receptor Norepinephrine Pharmacology Philosophy Psychology Receptor Synaptogenesis Treatment-resistant depression