PRIOR MORPHINE EXPOSURE ENHANCES IBOGAINE ANTAGONISM OF MORPHINE-INDUCED LOCOMOTOR STIMULATION

Ibogaine is currently being investigated for its potential use as an a nti-addictive agent. In the present study we sought to determine wheth er prior morphine exposure influences the ability of ibogaine to inhib it 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, IF) or saline and then received ibogaine (40 mg/kg, IF) 5 h af ter the last morphine pretreatment dose. Compared to rats pretreated w ith saline, rats pretreated with morphine (10, 20 or 30 mg/kg, IF) bef ore ibogaine (40 mg/kg, IF) showed a significant reduction in morphine -induced (5 mg/kg, IF) locomotor stimulation when tested 19 h after ib ogaine administration. Furthermore, this effect was apparent over a ra nge of ibogaine (5-60 mg/kg, IF) and morphine test (2.5-5 mg/kg, IF) d osages. Doses of ibogaine (5 and 10 mg/kg, IF) which alone were inacti ve inhibited morphine-induced locomotor activity when rats had been pr etreated with morphine. These results, showing that morphine pre-expos ure affects ibogaine activity, suggest that variable histories of opio id exposure might account for individual differences in the efficacy o f ibogaine to inhibit opioid addiction.