Summary

The CO2 inhalation challenge model is a robust tool for experimentally inducing panic attacks in order to test new anxiolytics. Patients with panic disorder are the most sensitive, with more than 90% experiencing a panic attack after inhaling CO2-enriched air, followed by healthy first-degree relatives of patients with panic disorder. Inhaling air enriched with CO2 triggers a panic attack in roughly half of healthy volunteers, making them the least sensitive population. Importantly, administering a therapeutic dose of clinically effective anxiolytic drugs such as benzodiazepines reduces the sensitivity to CO2-induced panic attacks in all such populations. Interestingly, CO2 inhalation can also induce robust fear-like behaviour in animal models, with physiological changes similar to changes measured in humans during a panic attack. Furthermore, the panic response induced by acutely inhaling CO2 remains stable and reproducible over time, which curtails concerns about the development of tolerance after repeated challenges. Also, the repeated inhalation of CO2 by healthy subjects who undergo the challenge carries no increased risk of developing a panic disorder. CO2 inhalation therefore represents a reliable, translational challenge model in the development of novel anxiolytic drugs.

CO2 inhalation challenge model

For psychiatric research, we acquired and calibrated a CO2 tolerance tester, which delivers a mixture of breathable air containing high CO2 levels and can measure a wide range of physiological parameters. CO2 inhalation can induce a panic attack in healthy volunteers and in patients with certain mood and/ or anxiety disorders. We use this so-called ‘CO2 inhalation challenge’ model to measure the anxiolytic/panicolytic effects of new test compounds.

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