CHOLECYSTOKININ AND ANXIETY IN NORMAL VOLUNTEERS - AN INVESTIGATION OF THE ANXIOGENIC PROPERTIES OF PENTAGASTRIN AND REVERSAL BY THE CHOLECYSTOKININ RECEPTOR SUBTYPE-B ANTAGONIST L-365,260

1 Two studies were undertaken to develop a model of experimentally ind uced anxiety in normal volunteers based on cholecystokinin (CCK) recep tor agonism/antagonism. 2 In Study 1 rapid intravenous injections of t he CCK receptor subtype B (CCKB) agonist pentagastrin (0.15, 0.3 and 0 .6 mu g kg(-1)) were found to produce dose-related increases in subjec tive ratings of anxiety compared with placebo. 3 In Study 2 the effect s of pre-treatment with two doses of the CCKB receptor antagonist L-36 5,260 (10 mg, 50 mg p.o.) on the anxiety induced by pentagastrin 0.3 m u g kg(-1) i.v. were investigated. Detailed measurements of blood pres sure and pulse rate were also undertaken. Pentagastrin produced change s in blood pressure and pulse rate which had a similar time course to that observed for subjective anxiety ratings. L-365,260 reversed both the autonomic and anxiogenic effects of pentagastrin. 4 The pentagastr in model would appear to be a useful tool for investigating potential anxiolytics in normal volunteers.