Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

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.