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 physiological functions such as thermoregulation and pain control. However, the possible interaction of cholecystokinin and morphine in epileptogenesis is unknown. We studied the effect of subcutaneous morphine and intracerebroventricularly administered cholecystokinin octapeptide sulphate ester 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 electrodes by a high voltage, high internal resistance constant current generator, 30 minutes after morphine administration and 10 minutes after cholecystokinin-8-SE, CCK-A and CCK-B infusion. Morphine decreased the length of the tonic component of the seizure and cholecystokinin potentiated this decrease. Cholecystokinin antagonists blocked the effects of both cholecystokinin and morphine. The results suggest that cholecystokinin acts as an endogenous agonist with opioids in the regulation of seizure susceptibility through both CCK-A and B receptors and may be responsible for part of the anticonvulsant action of morphine.
Legido
A
A
Department of Pediatrics, Temple University School of Medicine, Philadelphia, PA, USA.
Adler
M W
MW
Karkanias
C
C
Geller
E B
EB
Bradley
E
E
Greenstein
J I
JI
Grover
W D
WD
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects; D012640:Seizures; D012769:Shock
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D009020:Morphine; D002766:Cholecystokinin; D020109:Devazepide