Dr. Zanos, the Head of the Translational Neuropharmacology Lab, had the honor of presenting his research at the University of Athens as part of their Neuroscience Seminar Series.

In his talk titled “Decoding ketamine: Neurobiological mechanisms underlying its rapid antidepressant efficacy,” Dr. Zanos shared his team’s findings on ketamine’s unique properties as an antidepressant. He explained how ketamine differs from traditional treatments by producing relief from depressive symptoms within hours rather than weeks, though its widespread clinical use remains limited by side effects.

Dr. Zanos presented evidence challenging the conventional understanding that ketamine works primarily through NMDA receptor inhibition. His research demonstrates that other NMDAR antagonists such as MK-801 do not produce the same sustained antidepressant effects, pointing to a more nuanced mechanism.

During the seminar, he highlighted the significance of the (2R,6R)-hydroxynorketamine (HNK) metabolite, which exhibits antidepressant effects without ketamine’s typical side effects. Dr. Zanos discussed the surprising inverted U-shaped dose-response relationship his lab has discovered, suggesting that some level of NMDAR activation, rather than complete inhibition, may be optimal for antidepressant efficacy.

The presentation emphasized how both ketamine and (2R,6R)-HNK require AMPA receptor activation to exert their antidepressant effects, leading to synaptic potentiation and upregulation of specific AMPA receptor subunits. Furthermore, Dr. Zanos identified the NMDAR subunit GluN2A as playing an essential role in these processes.

The University of Athens faculty and students engaged in a productive discussion following the seminar, exploring the implications of this research for developing next-generation rapid-acting antidepressants with improved efficacy and reduced side effects.