Story perspectives

Ketamine Offers Rapid Antidepressant Effects via Adenosine Surge

4/14/2026

Summary

Story summary

Ketamine induces rapid antidepressant effects by triggering NMDA-independent adenosine surges in the medial prefrontal cortex, unlike traditional antidepressants that take weeks.
The mechanism reduces glutamate release and increases brain-derived neurotrophic factor (BDNF) levels via adenosine receptor signaling.
A1 and A2A receptors mediate the effect and A1 activation is linked to sustained antidepressant outcomes.
However, targeting A1 receptors carries systemic side-effect risks, so future strategies seek central A1 signaling with fewer cardiovascular risks.

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Story summary

Ketamine induces rapid antidepressant effects by triggering NMDA-independent adenosine surges in the medial prefrontal cortex, unlike traditional antidepressants that take weeks.
The mechanism reduces glutamate release and increases brain-derived neurotrophic factor (BDNF) levels via adenosine receptor signaling.
A1 and A2A receptors mediate the effect and A1 activation is linked to sustained antidepressant outcomes.
However, targeting A1 receptors carries systemic side-effect risks, so future strategies seek central A1 signaling with fewer cardiovascular risks.