[Potentiation of morphine- and ohmefentanyl-induced analgesia by cholecystokinin receptor antagonists in rat].
It has been reported that intrathecal (i.t.) injection of CCK-8 showed a marked antagonism to analgesic effects mediated by mu-opioid receptors in rat. The present study was performed to ascertain whether the blockade of endogenously released CCK-8 by potent and selective CCK-A antagonist devazepide and CCK-B antagonist L-365260 would affect opioid analgesia at the spinal cord level. A marked potentiation of the analgesic effect induced by morphine (4 mg/kg, sc) was produced by i.t. injection of 100 ng devazepide or 2.5 ng L-365260. Dose-response curves for the enhancement of the two drugs on morphine analgesia were bell-shaped. Intrathecal injection of 66 ng devazepide or 1.25 ng L-365260 was also shown to potentiate the analgesic effect induced by the selective mu-opioid agonist ohmefentanyl (OMF) (32 ng, i.t.). The dose-response curves were also bell-shaped. Devazepide or L-365260 per se produced no significant changes in rat tail flick latency (TFL). The above results are interpreted to mean that endogenously released CCK-8 in the spinal cord plays an antagonistic role to opioid analgesia, and it is the CCK-B receptors that mediate the anti-opioid effect since the dose of devazepide is 40-50 times higher than that of L-365260.
Zhou
Y
Y
Department of Physiology, Beijing Medical University.
Sun
Y H
YH
Han
J S
JS
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D020109:Devazepide; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects*; D010671:Phenylurea Compounds; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000502:physiology
D000700:Analgesics; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D009020:Morphine; C037016:F 7302; D020109:Devazepide; D005283:Fentanyl