Abstract
The neuropeptide cholecystokinin-tetrapeptide (CCK-4) has potent anxiogenic action in human and animal subjects. On the basis of prior work which demonstrated that benzodiazepine (BZD) receptor agonists antagonized CCK-induced excitation of rat hippocampal neurons we studied whether BZD receptors mediated the anxiogenic effect of CCK-4. To examine this possibility we determined whether the BZD receptor antagonist flumazenil could antagonize the effects of CCK-4 (50 µg) in healthy volunteers. Thirty subjects (10 females; 20 males) were pretreated with flumazenil (2 mg in saline) or placebo (0.9% NaCl in water) 15 min prior to CCK-4 challenge in a randomized double-blind crossover design. Flumazenil had no impact on the behavioral and cardiovascular effects of CCK-4, suggesting that BZD receptors do not mediate the anxiogenic action of CCK-4. The influence of GABA and non-GABA-related mechanisms on response to CCK-4 remains to be considered.
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Bradwejn, J., Koszycki, D., Couëtoux du Tertre, A. et al. Effects of flumazenil on cholecystokinin-tetrapeptide-induced panic symptoms in healthy volunteers. Psychopharmacology 114, 257–261 (1994). https://doi.org/10.1007/BF02244846
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DOI: https://doi.org/10.1007/BF02244846