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

Aims: To 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 Methods: Sixty-six C57BL/6J mice were pretreated with a KOR antagonist, nor-binaltorphimine (nor-BNI) (10mg·kg(-1)), or a normal saline placebo. All the mice received a subcutaneous injection of morphine (10mg·kg(-1)) 120min later and different doses of pentazocine (3, 10, 30, 56, 100mg·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 120min after the injection of morphine.

Key Findings: The tail pressure test, hot plate test and tail flick test showed that pentazocine at doses of 10 to 100mg·kg(-1), but not at 3mg·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 100mg·kg(-1) and morphine at 10mg·kg(-1).

Significance: High-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.