Rat aversion to isoflurane versus carbon dioxide

Some experts suggest that sedation of laboratory rodents with isoflurane before euthanasia with carbon dioxide (CO(2)) is a humane alternative to euthanasia with CO(2) alone, but little research has compared aversion with these agents. Albino rats were tested in a light-dark box where they had the choice between remaining in a dark compartment filling with isoflurane or CO(2), or escaping to a lit compartment. Experiment 1 validated the procedure by confirming that rats responded to agent and light intensity. In experiment 2, 9/16 and 0/16 rats remained in the dark compartment until recumbent when initially exposed to isoflurane and CO(2), respectively. In experiment 3, more rats remained in the dark compartment until recumbent during initial (10/16) versus re-exposure (1/16) to isoflurane. These results indicate that initial exposure to CO(2) is more aversive than isoflurane, and that re-exposure to isoflurane is more aversive than initial exposure. We conclude that sedation with isoflurane is a refinement over euthanasia with CO(2) alone for rats that have not been previously exposed to inhalant anaesthetics.