PEPTIDES AND ANXIETY - A DOSE-RESPONSE EVALUATION OF PENTAGASTRIN IN HEALTHY-VOLUNTEERS

A large body of data suggest that brain cholecystokinin (CCK) systems are involved in the regulation of anxiety, and numerous studies have d emonstrated that CCK-4, a CCKB agonist, reliably induces panic attacks in patients with panic disorder: Recently, pentagastrin, a commercial ly available CCKB agonist, has been reported to have similar anxiogeni c properties. To further explore the utility of pentagastrin as a chal lenge agent and to determine whether its effects are dose-related a do se-response study was conducted in ten healthy volunteers. Pentagastri n (0.2 mu g kg, 0.6 mu g/kg and 1.0 mu g/kg) and inactive placebo were infused over one minute on four separate challenge days in a double-b lind fashion. Subjects received pentagastrin while participating in a structured social interaction task. Repeated measures of anxiety, bloo d pressure, pulse, ACTH, and cortisol were taken at baseline and posti nfusion. Pentagastrin administration led to increases in anxiety, puls e, ACTH, cortisol and physical symptoms of panic, in a dose-related ma nner. Participation in the social interaction task led to increases in measures of anxiety as well as increases in pulse and blood pressure. Pew differences were found between the 0.2 mu g/kg dose of pentagastr in and placebo, or between the 0.6 mu g/kg and the 1.0 mu g/kg doses o f pentagastrin. These findings support the notion that CCK systems are involved in the regulation of anxiety, and suggest that the 0.6 mu g/ kg dose may be optimal for increasing symptoms of anxiety while minimi zing unpleasant side effects. The powerful anxiogenic effects of the s ocial interaction task underscore the importance of contextual variabl es in challenge studies. (C) 1995 Wiley-Liss, Inc.