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 micrograms) 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 micrograms); however, the DLH-induced flight behavior was not changed by similar central injections of CCK-4 (40, 4, or 0.4 micrograms). Peripheral injection of t-butoxycarbonyl (BOC)-CCK-4 (40 micrograms) 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.
Mongeau
R
R
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
Marsden
C A
CA
D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D010200:Panic / Q000187:drug effects* / Q000502:physiology; D010487:Periaqueductal Gray / Q000378:metabolism / Q000502:physiology*; D051381:Rats
D006710:Homocysteine; C007956:homocysteic acid; D002766:Cholecystokinin