[Potentiation of morphine- and ohmefentanyl-induced analgesia by cholecystokinin receptor antagonists in rat]

Abstract

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.