EFFECTS OF THE 5-HT3 ANTAGONIST, ONDANSETRON, ON THE BEHAVIORAL AND PHYSIOLOGICAL-EFFECTS OF PENTAGASTRIN IN PATIENTS WITH PANIC DISORDER AND SOCIAL PHOBIA

Pentagastrin, a cholecystokinin (CCK) agonist, produces anxiety and pa nic in patients with panic disorder and social phobia. Preclinical dat a suggests that pentagastrin-induced anxiogenesis may be mediated via 5-HT3 receptors. In the present study, 14 patients with panic disorder or social phobia underwent pharmacological challenge in three conditi ons: (1) pretreatment with saline followed by pentagastrin infusion; ( 2) pretreatment with ondansetron followed by pentagastrin infusion; an d (3) pretreatment with saline followed by saline infusion. As expecte d, pentagastrin administration led to increased anxiety, physical symp toms of panic attacks, pulse, plasma adrenocorticotropic hormone (ACTH ), and cortisol. Pentagastrin's behavioral effects were not blocked by ondansetron, and in fact, tended to be exaggerated, Ondansetron pretr eatment did not alter the pentagastrin-induced cortisol increase but s ignificantly prolonged the pentagastrin-induced increase in ACTH. Thes e findings suggest that pentagastrin's behavioral effects are not medi ated by 5HT(3) receptors. Mechanisms by which peripherally administere d CCK agonists lead to anxiety remain to be elucidated. Published by E lsevier Science Inc.