Anxiolyticlike effects of atrial natriuretic peptide on cholecystokinin tetrapeptide-induced panic attacks - Preliminary findings

Background: Panic attacks induced by administration of cholecystokinin tetr apeptide (CCK-4) have been evaluated as a valuable tool to investigate the neurobiological mechanisms involved in panic anxiety. The rationale to stud y the effects of natriuretic peptides on the CCK-4 response is derived from observations that atrial natriuretic peptide (ANP) is released during pani c attacks in humans and has anxiolyticlike actions in various animal models . Methods: A double-blind, placebo-controlled design was conducted in 9 patie nts with panic disorder and 9 similar healthy control subjects. After pretr eatment with an infusion of 150 mug of ANP or placebo in random order, each subject received 50 mug of CCK-4. Psychopathological parameters as well as physiological measures were sampled before and after CCK-4 administration. Results: After pretreatment with ANP, the number of CCK-4-induced panic att acks decreased from 8 to 6 in patients and from 5 to 2 in controls. Acute P anic Inventory ratings were significantly reduced in patients after ANP vs placebo pretreatment. Infusion of ANP significantly curtailed the CCK-4-ind uced release of corticotropin in patients. Heart rate variability analysis indicated a sympathetic stimulation by CCK-4 that was inhibited by ANP in p atients and controls. Conclusions The present study indicates that ANP exerts anxiolyticlike effe cts on CCK-4-stimulated anxiety attacks in patients with panic disorder. In addition, ANP produced an inhibition of the hypo thalamopituitary-adrenoco rtical system and sympatholytic effects.