A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsiaÐare central serotoninergic responses enhanced? T. G. DINAN*, N. MAHMUD  , O. RATHORE  , J. THAKORE§, L. V. SCOTT*, E. CARR à , J. NAESDAL à , C. A. O'MORAIN  & P. W. N. KEELING   *Department of Pharmacology and Therapeutics, University College Cork, Ireland;  Department of Gastroenterology, Trinity College Medical School, St James's and Tallaght Hospitals, Dublin, Ireland; àAstraZeneca R+D, Molndal and Dublin, Ireland; and §Department of Psychiatry, Royal College of Surgeons in Ireland Accepted for publication 4 June 2001 INTRODUCTION Dyspepsia is a common symptom ranging in prevalence from 26% in the USA to 41% in England. 1 While only one in four patients seeks medical help, 2 the condition results in signi®cant health care costs, 3 and an organic cause is found in only 40% of patients. The Rome criteria for diagnosing idiopathic or non-ulcer dyspepsia were originally put forward in 1991 and consist of chronic or recurrent upper abdominal pain or discom- fort in the absence of obvious pathology. 4 The Rome group suggested subcategorizing non-ulcer dyspepsia into ulcer-like, re¯ux-like, dysmotility-like and non- speci®c dyspepsia. The recent Rome II criteria provide a subgroup classi®cation based on the predominant symptom, and are supported by evidence suggesting SUMMARY Background: Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non-ulcer dyspepsia is made. The pathophysiology of non-ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity. Aim: To determine the sensitivity of serotonin receptors in non-ulcer dyspepsia. Methods: Using a randomized, double-blind, placebo- controlled design, we compared buspirone (a serotonin type 1a partial agonist)-stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was adminis- tered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart. Results: Overall, patients with non-ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most signi®cant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female sub- jects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females. Conclusions: Patients with non-ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Block- ade of such receptors might be an appropriate thera- peutic strategy. Correspondence to: Dr T. G. Dinan, Department of Pharmacology and Therapeutics, The Cork Clinic, Western Road, Cork, Ireland. E-mail: tdinan@indigo.ie Aliment Pharmacol Ther 2001; 15: 1613±1618. Ó 2001 Blackwell Science Ltd 1613