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 dors al periaqueductal grey area (DPAG), were used as an animal model to in vestigate this issue. CCK-4 (2 mu g) infused into the DPAG did not cha nge these panic-like reactions. The DLH-induced tachycardia was prolon ged by intracerebroventricular injection of CCK-4 (40 or 4 mu g) infus ed into the DPAG did not change these panic-like reactions. The DLH-in duced tachycardia was prolonged by intracerebroventricular injection o f CCK-4 (40 or 4 mu g): however, the DLH-induced flight behavior was n ot changed by similar central injections of CCK-4 (40, 4, or 0.4 mu g) . Peripheral injection of t-butoxycarbonyl (BOC)-CCK-4 (40 mu g) poten tiated the flight behavior, but did not alter the tachycardia response . It was concluded that CCK tetrapeptide potentiates panic-like behavi ors 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. (C) 1997 Socie ty of Biological Psychiatry.