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Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
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Depressant drugs, including alcohol and sedative-hypnotics, diminish central nervous system activity by enhancing the action of gamma-aminobutyric acid (GABA), a neurotransmitter that reduces brain activity and promotes relaxation. These substances can have various therapeutic uses but also pose significant risks, especially when misused or combined.
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Related Experiment Video

Updated: Feb 14, 2026

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Glutamatergic Modulators in Depression.

Ioline D Henter1, Rafael Teixeira de Sousa, Carlos A Zarate

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This summary is machine-generated.

Glutamatergic modulators show promise for treating depression. Research reviews evidence for various compounds, including ketamine and novel agents, offering new therapeutic avenues for mood disorders.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Glutamatergic system dysfunction is implicated in major depressive disorder and bipolar depression.
  • Subanesthetic ketamine doses rapidly reduce depressive symptoms, highlighting glutamate's role.

Purpose of the Study:

  • To review evidence for antidepressant effects of various glutamatergic modulators.
  • To explore novel therapeutic targets for mood disorders.

Main Methods:

  • Review of preclinical and clinical studies on glutamatergic modulators.
  • Categorization of modulators by mechanism of action.

Main Results:

  • Evidence supports antidepressant effects of broad modulators (ketamine, esketamine, dextromethorphan).
  • Investigational drugs targeting NMDA receptors, glycine sites, and mGluRs show potential.

Conclusions:

  • Glutamatergic modulators represent a promising class of antidepressants.
  • Further research into these agents may lead to novel treatments for mood disorders.