To provide a basis for the use of the CCK-4 model in proof-of-concept studies, we investigated CCK-4-induced panic according to different criteria in 85 healthy volunteers who underwent a CCK-4 bolus injection.
Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) has been established as a model to study the pathophysiology of panic disorder and might serve as a tool to asses the antipanic potential of novel anxiolytic compounds.
CCK-4-induced panic attacks were less frequent after prior exercise: they occurred in 15 (62.5%) subjects after rest (9 patients and 6 control subjects), but only 5 (20.8%) subjects after exercise (4 patients and 1 control subject).
The effects of CCK-4 (25 microg in patients and 50 microg in control subjects) were measured with the Acute Panic Inventory (API) score, comparing panic attack frequencies, total score, and subscores for anxiety and somatic symptoms.
The effects of quiet rest or an aerobic treadmill exercise (30 min at an intensity of 70% of the maximal oxygen uptake, VO2max) on cholecystokinin tetrapeptide (CCK-4) induced panic attacks were studied in a crossover design in 12 patients with panic disorder and 12 matched healthy subjects.
Moreover, a reduction of CCK-4-induced panic has also been demonstrated after treatment with lorazepam in single subjects and after selective GABAergic treatment with vigabatrin.
In conclusion, our data show that alprazolam reduces CCK-4-induced panic, which supports the hypothesis of a possible interaction between the GABA and the CCK system.
Although benzodiazepines are widely used as anxiolytics, no controlled study on the effects of benzodiazepines on CCK-4-induced panic symptoms is available so far.
Therefore, we investigated the effects of alprazolam and placebo on CCK-4-induced panic symptoms in a double-blind, placebo-controlled study.
Other polymorphisms previously associated with PD were unrelated to CCK-4-induced panic attacks, probably due to the differences between complex nature of PD and laboratory panic model.
None of the other candidate loci were significantly associated with CCK-4-induced panic attacks in healthy subjects.
In this study we aimed to explore the effects of several genetic polymorphisms previously implicated in PD on the susceptibility to cholecystokinin-tetrapeptide (CCK-4) challenge in healthy subjects.
Panic induced by cholecystokinin tetrapeptide was significantly more pronounced in the short/short genotype subjects under escitalopram vs. placebo pre-treatment.
Contrary to our expectation, no inhibitory effect of escitalopram upon panic symptoms elicited by choleystokinin tetrapeptide could be demonstrated in healthy men.
The primary outcome measure was the increase of Acute Panic Inventory ratings by cholecystokinin tetrapeptide.
Panic attacks induced by administration of cholecystokinin tetrapeptide (CCK-4) have been evaluated as a valuable tool to investigate the neurobiological mechanisms involved in panic anxiety.
The present study indicates that ANP exerts anxiolyticlike effects on CCK-4-stimulated anxiety attacks in patients with panic disorder.
Sensitivity to the panicogenic effects of cholecystokinin-tetrapeptide (CCK-4) is enhanced in panic disorder patients relative to normal controls (NC).
Demonstrating that the effects of CCK-4 are reproducible in panic patients opens the doors for studies of the effects of drug treatment on CCK-4-induced panic.
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