Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats

Abstract

Carbon dioxide (CO₂) is commonly used to kill laboratory rats. Rats find CO₂ aversive and aversion varies between individuals, indicating that rats vary in CO₂ sensitivity. Healthy humans experience feelings of anxiety at concentrations similar to those avoided by rats, and these feelings are diminished by the administration of benzodiazepines. Our aim was to assess the effects of the benzodiazepine midazolam on individual thresholds of rat aversion to CO₂. Six female Sprague Dawley rats were repeatedly exposed to CO₂ gradual-fill in approach-avoidance testing. The first three exposures were to a control-treatment followed by three exposures to midazolam (0.375 mg/kg). Within each treatment aversion to CO₂ was not affected by exposure number; however, tolerance increased from an average of 10.7% CO₂ avoided during control sessions, to 15.5% CO₂ avoided when treated with midazolam. These results indicate that rats experience anxiety when exposed to CO₂, and that variation in rat CO₂ sensitivity is driven by individual differences in the onset of these feelings of anxiety. No rat tolerated CO₂ concentrations required to induce loss of consciousness.