Effect of repeat exposure on neuroendocrine and symptom responses to pentagastrin

The cholecystokinin (CCK-B) agonist pentagastrin stimulates dose-dependent release of adrenocorticotropin (ACTH) and cortisol in humans, likely via direct pharmacological action at pituitary CCK-B receptors. Pentagastrin also produces side effects, however, which may be experienced as novel or anxiety arousing and could contribute to ACTH release. Available data suggest that pentagastrin's activation of the hypothalamic-pituitary-adrenal (HPA) axis is unrelated to anxiety symptoms themselves, but novelty effects have not been examined in this model and do strongly activate this system in animals. To further explore the impact of novelty and anxiety symptoms on HPA responses, pentagastrin was administered twice to 12 subjects (six male, six female) under single-blind conditions. Repeat pentagastrin injection was associated with a slight habituation in the magnitude of symptom and HPA axis responses, but robust HPA and symptom responses were seen following both injections. No relationships were found between anxiety symptoms and HPA activity and the modest symptomatic and neuroendocrine habituation appeared to occur independently. Pentagastrin may release ACTH and cortisol through direct pharmacological action, perhaps enhanced on first exposure by psychologically mediated novelty effects. Novelty, per se, is not likely the primary mediator of the HPA response. This model may be useful for further study of cognitive-emotional modulators of HPA axis activity.