A 28-year-old woman with treatment-resistant major depression undergoes intranasal esketamine therapy. The mechanism of its rapid antidepressant effect is:

• A Rapid SERT blockade causing acute serotonin burst in limbic system synapses
• B AMPA receptor-mediated synaptic potentiation via BDNF release and TrkB activation ✓
• C Blockade of NMDA receptors at rest (when blocked by Mg2+), relieving synaptic depression
• D Inhibition of glutamate reuptake transporter EAAT2, prolonging AMPA receptor activation

Explanation

Esketamine (the S-enantiomer of ketamine) blocks NMDA receptors, particularly extrasynaptic NMDARs on GABAergic interneurons, disinhibiting glutamate release. The resulting AMPA receptor activation stimulates BDNF (brain-derived neurotrophic factor) release and TrkB receptor signalling, which activates mTORC1 pathway to rapidly increase synaptogenesis and restore atrophied dendritic spines in the prefrontal cortex and hippocampus. This synaptic plasticity underlies the rapid (within hours) antidepressant effect — far faster than classical antidepressants.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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