[Cholecystokinin octapeptide (CCK-8) antagonized analgesia mediated by mu and kappa opioid receptors]

Abstract

CCK-8 has been shown to antagonize the analgesia produced by morphine or endogenous opioid peptides. The present study was performed to clarify the interaction between CCK-8 and different opioid ligands. Analgesia produced by intrathecal (I.T.) injection of the specific mu receptor agonist PL017 10 ng or kappa receptor agonist NDAP 500 ng can be antagonized by I.T. injection CCK-8 at a dose as small as 4 ng. In contrast, analgesia produced by I.T. injection of the delta receptor agonist DPDPE (6.5, 13 and 26 micrograms) was not blocked by CCK-8 (4 ng or 40 ng, I.T.). The antagonistic effect of CCK-8 on PL017 and NDAP could be completely reversed by proglumide (3 micrograms, I.T.). I.T. injection of CCK-8 (4 or 40 ng single dose or cumulative dose of 0.1, 0.2, 0.5 and 1.0 microgram at 10 min intervals) produced neither analgesia nor hyperalgesia. In conclusion, CCK-8 preferentially antagonizes opioid analgesia mediated by mu and kappa receptors, and this antagonistic effect is mediated by CCK receptors.