THE HISTORY of the investigation of the neurobiology of panic disorder is largely the history of the pharmacologic challenge paradigm. Beginning with the 1968 report of Pitts1 that sodium lactate could provoke panic attacks, the physiologic and psychologic effects of lactate infusion in patients with panic disorder were intensively investigated for the next 2 decades. Interest in noradrenergic agents such as yohimbine and isoproterenol began in the 1980s along with caffeine and carbon dioxide (CO2). In the last decade, interest in these disparate panicogenic challenge paradigms has gradually converged on the CO2 inhalation procedure,2 largely because of its ease and brevity of administration in conjunction with the known physiology of this manipulation.
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