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

Carbon dioxide (CO) is commonly used to kill laboratory rats. Rats find CO aversive and aversion varies between individuals, indicating that rats vary in CO 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 CO. Six female Sprague Dawley rats were repeatedly exposed to CO 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 CO was not affected by exposure number; however, tolerance increased from an average of 10.7% CO avoided during control sessions, to 15.5% CO avoided when treated with midazolam. These results indicate that rats experience anxiety when exposed to CO, and that variation in rat CO sensitivity is driven by individual differences in the onset of these feelings of anxiety. No rat tolerated CO concentrations required to induce loss of consciousness.