CHOLECYSTOKININ POTENTIATES MORPHINE ANTICONVULSANT ACTION THROUGH BOTH CCK-A AND CCK-B RECEPTORS

Recent studies have suggested that cholecystokinin may have a role in modulating the effects of the endogenous opioid system in physiologica l functions such as thermoregulation and pain control. However, the po ssible interaction of cholecystokinin and morphine in epileptogenesis is unknown. We studied the effect of subcutaneous morphine and intrace rebroventricularly administered cholecystokinin octapeptide sulphate e ster and receptor antagonists CCK-A (MK 329) and CCK-B (L 365,260) on seizures provoked by maximal electroshock in male Sprague-Dawley rats. Seizures were induced through electrode-gel-coated ear clip electrode s by a high voltage, high internal resistance constant current generat or, 30 minutes after morphine administration and 10 minutes after chol ecystokinin-8-SE, CCK-A and CCK-B infusion. Morphine decreased the len gth of the tonic component of the seizure and cholecystokinin potentia ted this decrease. Cholecystokinin antagonists blocked the effects of both cholecystokinin and morphine. The results suggest that cholecysto kinin acts as an endogenous agonist with opioids in the regulation of seizure susceptibility through both CCK-A and B receptors and may be r esponsible for part of the anticonvulsant action of morphine.