Pentobarbital antagonism of morphine analgesia mediated by spinal cholecystokinin

Pentobarbital administered intracerebroventricularly to mice has been shown previously to inhibit the analgesic action of morphine given intrathecally. The purpose of the present study was to examine the proposal that this antianalgesic action was mediated spinally by cholecystokinin. First, intrathecal coadministration of cholecystokinin-8 sulfate (CCK8s) with morphine inhibited the analgesic action of morphine in the mouse tail-flick test. This rightward shift of the morphine dose-response curve was reversed by the intrathecal administration of either the CCKA receptor antagonist, lorglumide, or the CCKB receptor antagonist, PD135,158. Second, lorglumide and PD135,158 given intrathecally also eliminated the antianalgesic effect of intracerebroventricularly administered pentobarbital against intrathecal morphine. Third, intrathecal pretreatment with CCK8 antiserum eliminated the effect of pentobarbital. Thus, the results indicated that pentobarbital antianalgesia was obtained through activation of a descending system to the spinal cord where cholecystokinin inhibited the spinal analgesic action of morphine.