EFFECTS OF FLUMAZENIL ON CHOLECYSTOKININ-TETRAPEPTIDE-INDUCED PANIC SYMPTOMS IN HEALTHY-VOLUNTEERS

The neuropeptide cholecystokinin-tetrapeptide (CCK-4) has potent anxio genic action in human and animal subjects. On the basis of prior work which demonstrated that benzodiazepine (BZD) receptor agonists antagon ized CCK-induced excitation of rat hippocampal neurons we studied whet her BZD receptors mediated the anxiogenic effect of CCK-4. To examine this possibility we determined whether the BZD receptor antagonist flu mazenil could antagonize the effects of CCK-4 (50 mu g) in healthy vol unteers. Thirty subjects (10 females; 20 males) were pretreated with f lumazenil (2 mg in saline) or placebo (0.9% NaCl in water) 15 min prio r to CCK-4 challenge in a randomized double-blind crossover design. Fl umazenil had no impact on the behavioral and cardiovascular effects of CCK-4, suggesting that BZD receptors do not mediate the anxiogenic ac tion of CCK-4. The influence of GABA and non-GABA-related mechanisms o n response to CCK-4 remains to be considered.