These data suggest that CCKB receptors are an important site of action of exogenous CCK-4. It will be important to determine in future studies the efficacy of CCKB receptor antagonists as antipanic agents.
It has been suggested that cholecystokinin, a neurotransmitter found in high density in mammalian brain, might be implicated in the neurobiology of panic and anxiety disorders. Cholecystokinin-tetrapeptide induces panic attacks analogous to spontaneous panic attacks in patients suffering from panic disorder and to a much lesser degree in healthy volunteers, suggesting an enhanced sensitivity to cholecystokinin-tetrapeptide in panic disorder. In animal models of anxiety, pre-treatment with cholecystokinin antagonists significantly decreases the anxiogenic effects of cholecystokinin agonists. This paper reviews clinical and basic studies supporting an involvement for cholecystokinin in panic and anxiety disorders.
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 micrograms) 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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