Effects of ibogaine on the development of tolerance to antinociceptive action of mu-, delta- and kappa-opioid receptor agonists in mice.

Ibogaine, a compound from the African shrub Tabernanthe iboga, selectively blocks the development of tolerance to morphine's pain-relieving effect in male Swiss-Webster mice. Mice given morphine, U-50,488H, or DPDPE (agonists for mu-, kappa-, and delta-opioid receptors, respectively) twice daily for four days became tolerant to these drugs' antinociceptive effects. Ibogaine at 40 or 80 mg/kg, given before each morphine injection, prevented tolerance to morphine, but 20 mg/kg did not. Ibogaine did not affect tolerance to kappa- or delta-receptor agonists at any dose. The results suggest ibogaine specifically inhibits tolerance to mu-opioid receptor agonists.

Study at a glance

Abstract

The effects of ibogaine, an alkaloid isolated from the bark of the African shrub, Tabernanthe iboga, on the development of tolerance to the antinociception action of morphine, U-50,488H and [D-Pen2,D-Pen5]enkephalin (DPDPE), which are mu-, kappa- and delta-opioid receptor agonists, respectively, were determined in male Swiss-Webster mice. Mice were rendered tolerant to opioid receptor agonists by injecting morphine (20 mg/kg, s.c.), U-50,488H (25 mg/kg, i.p.) or DPDPE (20 microg/mouse, i.c.v.) twice a day for 4 days. Ibogaine (20, 40 or 80 mg/kg, i.p.) given twice a day for 4 days did not alter the tail-flick latency. Ibogaine (40 or 80 mg/kg, i.p.) injected 10 min before each injection of morphine inhibited the development of tolerance to the antinociceptive action of morphine, however, the lower dose of ibogaine (20 mg/kg, i.p.) was ineffective. Ibogaine (20, 40 or 80 mg/kg, i.p.) given prior to the injection of U-50,488H or DPDPE did not modify the development of tolerance to their antinociceptive action. It is concluded that ibogaine inhibits selectively the development of tolerance to the antinociceptive action of mu- but not kappa- or delta-opioid receptor agonists in mice.