| Abstract: | Ibogaine is an kndole alkaloid that has bean suggested to have potential efficacy for internrpdng dependermy on stimulant drugs. The κ-opiold and serotonkr 5-HT3 systems may be involved in the action of Ibogaine, related to their modulation of dopaminergic transmission. The κ-opioid agonist U 62066 attenuated the in vitrostimulation-evoked efflux of tritium label from striatal tissue prelabeled with (3H)dopamine. In mice protreated with Ibogaine·HCl (40 mg/kg IP given 2 h prior or 2 × 40 mg/kg and animals killed 18 h later), the Inhibitory effect of U 62066 on stimulation-evoked release of tritium was eliminated. The 5-HT3 agonist phernylbiguanide had a biphasic effect on stimulation-evoked release of tritium; at 10−6 M phenylbiguanide, stimulation-evoked release was attenuated. At 10−5 M the basal outflow of tritium was increased. Ibogaine pretreatment had no effect on basal or stimulation-evokedrelease in the presence of 10−6 M phenylbiguanide, but increased the stimulation-evoked outflow of bftkan in the presence of 10−5 M phenylbiguanide. Cocaine (10−6 M), a dopanlne uptake blocker, increased the electrically-evoked release of dopamine; ibogaine pretreatment did not affect the enhanced electrically-induced release of (3H]dopamine by in vitro cocalne. The effects of ibogaine on the κ-opioid and 5-HT3 receptors, located presynaptically on stristal dopamine terminals, modulating dopamine release may partly underlie its putative antiaddictive properties. |
