Antinociceptive effects of morphine and U-50,488h on vaginal distension in the anaesthetized rat

Abstract

The antinociceptive activity of the k- and μ-opioid receptor agonists, (±)-U-50,488H and morphine, was examined in a vaginal distension model in anaesthetized female rats. Vaginal distension induced a reproducible cardiovascular response (CVR) which was inhibited in a dose related manner by morphine ( 0.03 − 1.0 mg kg i.v., ED 50 = 0.16 mg kg ) and (±)-U-50,488H ( 0.08−1.6 mg kg i.v., ED 50 = 0.49 mg kg ). Morphine (0.3 μg/rat) administered i.c.v. inhibited the CVR by 81.6 ± 7.9% whereas (±)-U-50,488H (30–300 μg/rat) was inactive by this route. A low dose of naloxone (30 μg kg i.v.) blocked the effect of morphine but not that of (±)-U- 50, 488H. The k-opioid antagonist, nor-binaltorphimine (10 mg kg s.c.) abolished the response to (±)-U-50,488H but not that of morphine. This demonstrates that both central and peripheral μ-opioid receptors may be involved in morphine-induced antinociception whereas the k-opioid agonist, (±)-U-50,488H, blocks vaginal nociception by acting on peripheral k-opioid receptors.