Caerulein-induced antinociception: interaction with morphine and opioid antagonists in the rat

The relationship between CCK- and opioid-activated systems in antinociception is not clear. The effects of morphine, naloxone and naltrexone on the antinociceptive effect of systemically administered caerulein was determined using the paw pressure test in the rat. Caerulein treatment significantly increased paw pressure threshold with an ED50 of 30 micrograms/kg (22.2 nmol/kg) and was considerably more potent than morphine in this respect (ED50 of 882 nmol/kg). The opioid antagonists naloxone and naltrexone were found to potentiate the antinociceptive effect of caerulein (30 micrograms/kg) whilst abolishing the effect of morphine at doses of 3 micrograms/kg and above. Co-administration of caerulein (30 micrograms/kg) with low doses of morphine, normally ineffective in the paw pressure test, abolished caerulein-induced antinociception. However the effects of antinociceptive doses of morphine were depressed by caerulein (30 micrograms/kg), showing a mutual antagonism between caerulein and opioid activated effects. In contrast to these observations, morphine pre-injection (3h before testing) was found to significantly potentiate caerulein-induced antinociception revealing a differential interaction between opioid and CCK systems at different time points. The results indicate that CCK and opioids produce antinociception by separate, yet overlapping mechanisms.