Given the anxiogenic effects of the type-B natriuretic peptide receptor agonist C-type natriuretic peptide (CNP) in rodents, we investigated the influence of CNP pretreatment upon the behavioral and endocrine action of the panicogen cholecystokinin tetrapeptide (CCK-4) in healthy men. In a randomized double-blind balanced design, 20 male volunteers were given an intravenous infusion of 300 microg of CNP vs. placebo followed by 25 microg of CCK-4. The behavior was assessed using panic, anxiety, and dissociation questionaires before the infusion and after the CCK-4 stimulus. Furthermore, the stress-sensitive hormones adrenocorticotropic hormone (ACTH), cortisol, and prolactin were measured. CNP pretreatment enhanced the anxiogenic and prodissociative effects of CCK-4 and significantly augmented the ACTH surge after CCK-4. However, no effect of CNP was seen upon panic symptoms. Our preliminary data support a role of type-B natriuretic peptide receptors in anxiety modulation in normal man.
