High-dose pentazocine antagonizes the antinociception induced by high-dose morphine

ABSTRACTAimsTo investigate the effects of high doses of pentazocine on antinociception induced by a high dose of morphine and the role of the kappa-opioid receptors (KORs) in these effects in mice.Main methodsSixty-six C57BL/6J mice were pretreated with a KOR antagonist, nor-binaltorphimine (nor-BNI) (10 mg·kg− 1), or a normal saline placebo. All the mice received a subcutaneous injection of morphine (10 mg·kg− 1) 120 min later and different doses of pentazocine (3, 10, 30, 56, 100 mg·kg− 1) or a normal saline placebo. A tail pressure test, hot plate test and tail flick test were performed before and at 30, 60, 90 and 120 min after the injection of morphine.Key findingsThe tail pressure test, hot plate test and tail flick test showed that pentazocine at doses of 10 to 100 mg·kg− 1, but not at 3 mg·kg− 1, had significant antagonizing effects on the antinociception induced by high-dose morphine to mechanical and thermal pain, and nor-BNI did not affect antinociception in combination with pentazocine at 10 to 100 mg·kg− 1 and morphine at 10 mg·kg− 1.SignificanceHigh-doses of pentazocine antagonize the antinociception induced by a high-dose of morphine in a dose-dependent manner, and this antagonistic effect is not associated with the activation of KORs.