Effects of the 5-HT3 antagonist, ondansetron, on the behavioral and physiological effects of pentagastrin in patients with panic disorder and social phobia

Una D. McCann, Christina M. Morgan, Marilla Geraci, Shiyoko O. Slate, Dennis L. Murphy, Robert M. Post

Research output: Contribution to journalArticle

Abstract

Pentagastrin, a cholecystokinin (CCK) agonist, produces anxiety and panic in patients with panic disorder anti social phobia. Preclinical data 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 conditions: (1) pretreatment with saline followed by pentagastrin infusion; (2) pretreatment with ondansetron followed by pentagastrin infusion; and (3) pretreatment with saline followed by saline infusion. As expected, pentagastrin administration led to increased anxiety, physical symptoms 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 pretreatment did not alter the pentagastrin-induced cortisol increase but significantly prolonged the pentagastrin-induced increase in ACTH. These findings suggest that pentagastrin's behavioral effects are not mediated by 5HT3 receptors. Mechanisms by which peripherally administered CCK agonists lead to anxiety remain to be elucidated.

Original languageEnglish (US)
Pages (from-to)360-369
Number of pages10
JournalNeuropsychopharmacology
Volume17
Issue number6
DOIs
StatePublished - Dec 1 1997
Externally publishedYes

Keywords

  • Anxiety disorders
  • Cholecystokinin (CCK)
  • Neuropeptides
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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