DIFFERENTIAL-EFFECTS OF SULFATED CHOLECYSTOKININ OCTAPEPTIDE AND PROGLUMIDE INJECTED INTRATHECALLY ON ANTINOCICEPTION INDUCED BY BETA-ENDORPHIN AND MORPHINE ADMINISTERED INTRACEREBROVENTRICULARLY IN MICE

The effects of sulfated cholecystokinin octapeptide (CCK-8s) and CCK-8s antagonist, proglumide, given intrathecally (i.t.) on inhibition of the tail-flick and hot-plate paw-licking responses induced by β-endorphin and morphine given intracerebroventricularly (i.c.v.) were studied in male ICR mice. Both CCK-8s (up to 0.5 ng) and proglumide (up to 10 μg) injected alone did not affect significantly the control latencies of the tail-flick and paw-licking responses. I.t. injection of CCK-8s as doses from 0.125 to 0.5 ng dose dependently attenuated inhibition of the tail-flick response induced by i.c.v. administered β-endorphin. The antagonistic effect of CCK-8s on β-endorphin-induced inhibition was blocked by the co-i.t. injection of proglumide (0.1-1 μg) in a dose-dependent manner. High doses 2.5-10 μg) of proglumide given i.t. dose dependently enhanced inhibition of the tail-flick response induced by i.c.v. administered β-endorphin. However, i.t. injection of CCK-8s and proglumide did not affect inhibition of the paw-licking response induced by i.c.v. administered β-endorphin. The inhibitions of the tail-flick and paw-licking responses induced by i.c.v. administered morphine were not affected by i.t. injection of CCK-8s or proglumide. Our results suggest that CCK-8s in the spinal cord may play an important modulatory role in attenuating the descending pain inhibition induced by i.c.v. administered β-endorphin but not morphine. © 1990.