Panic-like escape response elicited in mice by exposure to CO2, but not hypoxia

Abstract

Exposure to elevated concentrations of CO2 or hypoxia has been widely used in psychiatric research as a panic provoking stimulus. However, the use of these respiratory challenges to model panic-like responses in experimental animals has been less straightforward. Little data is available, from behavioral and endocrine perspectives, to support the conclusion that a marked aversive situation, such as that experienced during panic attacks, was evoked in these animals. We here compared the behavioral responses of male CB57BL/6 mice during exposure to 20% CO2 or 7% O2 and its consequence on plasma levels of corticosterone. We also evaluated whether clinically-effective panicolytic drugs affect the behavioral responses expressed during CO2 exposure. The results showed that whereas hypoxia caused a marked reduction in locomotion, inhalation of CO2-enriched air evoked an active escape response, characterized by bouts of upward leaps directed to the border of the experimental cage, interpreted as escape attempts. Corticosterone levels were increased 30 min after either of the respiratory challenges used, but it was higher in the hypoxia group. Chronic (21 days), but not acute, treatment with fluoxetine or imipramine (5, 10 or 15 mg/kg) or a single injection of alprazolam (0.025, 0.05 or 0.1 mg/kg), but not of the anxiolytic diazepam (0.025, 0.05 or 0.1 and 1 mg/kg) reduced the number of escape attempts, indicating a panicolytic-like effect. Altogether, the results suggest that whereas hypoxia increased anxiety, exposure to 20% CO2 evoked a panic-like state. The latter condition/test protocol seems to be a simple and validated model for studying in mice pathophysiological mechanisms and the screening of novel drugs for panic disorder.