Effect of central and peripheral administrations of cholecystokinin—tetrapeptide on panic-like reactions induced by stimulation of the dorsal periaqueductal grey area in the rat

Administration of cholecystokinin—tetrapeptide (CCK-4) triggers panic attacks in humans, but it is not known whether CCK-4 acts in the brain to produce this effect. Panic-like reactions (flight and tachycardia) induced in rats by injecting D,L-homocysteic acid (DLH) into the dorsal periaqueductal grey area (DPAG), were used as an animal model to investigate this issue. CCK-4 (2 μg) infused into the DPAG did not change these panic-like reactions. The DLH-induced tachycardia was prolonged by intracerebroventricular injection of CCK-4 (40 or 4 μg); however, the DLH-induced flight behavior was not changed by similar central injections of CCK-4 (40, 4, or 0.4 μg). Peripheral injection of t-butoxycarbonyl (BOC)-CCK-4 (40 μg) potentiated the flight behavior, but did not alter the tachycardia response. It was concluded that CCK tetrapeptide potentiates panic-like behaviors by acting on a peripheral target or on a circumventricular area of the brain. In contrast, increased brain CCK-4 prolongs tachycardia by acting in the brain at a level distinct from the DPAG.