Prior morphine exposure enhances ibogaine antagonism of morphine-induced locomotor stimulation.

Prior morphine exposure enhances ibogaine's ability to reduce morphine-induced locomotor stimulation in female rats. Rats pretreated with morphine (10, 20, or 30 mg/kg) before receiving ibogaine (40 mg/kg) showed significantly less locomotor activity when later given morphine (5 mg/kg), compared to rats pretreated with saline. This effect occurred across a range of ibogaine (5–60 mg/kg) and morphine test (2.5–5 mg/kg) doses. Even low ibogaine doses (5 and 10 mg/kg) that alone had no effect became effective after morphine pretreatment. The findings suggest that an individual's history of opioid exposure may influence ibogaine's efficacy against opioid addiction.

Study at a glance

Abstract

Ibogaine is currently being investigated for its potential use as an anti-addictive agent. In the present study we sought to determine whether prior morphine exposure influences the ability of ibogaine to inhibit morphine-induced locomotor stimulation. Female Sprague-Dawley rats were pretreated once a day for 1-4 days with morphine (5, 10, 20 or 30 mg/kg, i.p.) or saline and then received ibogaine (40 mg/kg, i.p.) 5 h after the last morphine pretreatment dose. Compared to rats pretreated with saline, rats pretreated with morphine (10, 20 or 30 mg/kg, i.p.) before ibogaine (40 mg/kg, i.p.) showed a significant reduction in morphine-induced (5 mg/kg, i.p.) locomotor stimulation when tested 29 h after ibogaine administration. Furthermore, this effect was apparent over a range of ibogaine (5-60 mg/kg, i.p.) and morphine test (2.5-5 mg/kg, i.p.) dosages. Doses of ibogaine (5 and 10 mg/kg, i.p.) which alone were inactive inhibited morphine-induced locomotor activity when rats had been pretreated with morphine. These results, showing that morphine pre-exposure affects ibogaine activity, suggest that variable histories of opioid exposure might account for individual differences in the efficacy of ibogaine to inhibit opioid addiction.