Cholecystokinin octapeptide antagonized opioid analgesia mediated by mu- and kappa- but not delta-receptors in the spinal cord of the rat.

Intrathecal (ith) injection of cholecystokinin octapeptide (CCK-8) to the rat with single dose of 4 or 40 ng, or successive doses from 0.1 to 1 microgram at 10 min intervals produced neither analgesia nor hyperalgesia. However, the analgesia produced by ith injection of PL017, a specific mu-receptor agonist or 66A-078, a specific kappa-receptor agonist could be markedly antagonized by CCK-8 at a dose as small as 4 ng. In contrast, analgesia produced by ith injection of delta-agonist DPDPE could not be blocked by CCK-8 even at a dose as high as 40 ng. Since the effect of CCK-8 could be totally reversed by the CCK receptor antagonist proglumide, this effect is most probably mediated by CCK receptors.