[Cholecystokinin-octapeptide antagonizes the central depressive effect of opioid peptides in rats]

Cholecystokinin-octapeptide (CCK-8) has been shown to antagonize the analgesia produced by opioid peptides. The present study was performed to evaluate its effect on cardiovascular regulatory functions of opioids. Both CCK-8 and opioid peptides were injected intrathecally (ith) in pentobarbital anaesthetized rats. The depressive effects induced by the mu agonist PL017 (5 micrograms), delta agonist DADLE (25 micrograms) and kappa agonist 66A-078 (1 microgram) were antagonized by CCK-8 within a dosage of 10 micrograms in a dose dependent manner. CCK-8 can also partly antagonize the bradycardiac effects induced by PL017, DADLE and 66A-078. The antagonistic effect of CCK-8 on DADLE in MAP could be reversed by pretreatment with CCK receptor antagonist proglumide (100 micrograms). No significant changes in MAP were found following ith administration of CCK-8 0.5-10 micrograms and proglumide 100 micrograms, but a large dose (50 micrograms) of CCK-8 lowered MAP dramatically. The results suggest that within a certain range of dose CCK-8 in spinal cord may play an antagonistic role against opioid effects in the regulation of cardiovascular function and this effect of CCK-8 seems to be mediated by CCK receptor. These results support the hypothesis that CCK-8 may act as an anti-opioid substance in the CNS of the rat.