A review of behavioral and pharmacologic studies relevant to the application of CO₂ as a human subject model of anxiety

Most applications of a model of anxiety in human subjects would require at minimum a method of inducing a behavioral state in humans that descriptively resembles clinical anxiety and that responds to pharmacologic interventions in a manner similar to clinical anxiety. Ideally, the neuronal mechanisms affected by the model's anxiety-inducing agent would also be similar to those underlying clinical anxiety. The purpose of this paper is to review evidence from our laboratory and elsewhere that inhalation of elevated levels of carbon dioxide may produce a behavioral state meeting the descriptive and pharmacologic requirements. Review of the neurobiologic effects of CO₂ and their relation to the pathophysiology of anxiety is beyond the scope of this paper. The potential usefulness of CO₂ as a model of anxiety and directions for future studies will be discussed.