The effect of ibogaine on kappa-opioid- and 5-HT3-induced changes in stimulation-evoked dopamine release in vitro from striatum of C57BL/6By mice.

Ibogaine, an indole alkaloid, may help interrupt stimulant drug dependency by affecting dopamine release in the brain's striatum. In mouse striatal tissue, the kappa-opioid agonist U 62066 reduced stimulated dopamine release, but ibogaine pretreatment (40 mg/kg IP given 2 hours prior or 2 x 40 mg/kg with animals killed 18 hours later) eliminated this effect. The 5-HT3 agonist phenylbiguanide had a biphasic effect: at 10(-6) M it reduced release, while at 10(-5) M it increased basal outflow. Ibogaine pretreatment did not alter release with 10(-6) M phenylbiguanide but increased stimulated outflow with 10(-5) M. Cocaine (10(-6) M) increased electrically-evoked dopamine release, and ibogaine did not affect this. Ibogaine's modulation of kappa-opioid and 5-HT3 receptors on dopamine terminals may underlie its antiaddictive properties.

Study at a glance

Abstract

Ibogaine is an indole alkaloid that has been suggested to have potential efficacy for interrupting dependency on stimulant drugs. The kappa-opioid and serotonin 5-HT3 systems may be involved in the action of ibogaine, related to their modulation of dopaminergic transmission. The kappa-opioid agonist U 62066 attenuated the in vitro stimulation-evoked efflux of tritium label from striatal tissue prelabeled with [3H]dopamine. In mice pretreated with ibogaine.HCI (40 mg/kg IP given 2 h prior or 2 x 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 phenylbiguanide 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-evoked release in the presence of 10(-6) M phenylbiguanide, but increased the stimulation-evoked outflow of tritium in the presence of 10(-5) M phenylbiguanide. Cocaine (10(-6) M), a dopamine 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 cocaine. The effects of ibogaine on the kappa-opioid and 5-HT3 receptors, located presynaptically on striatal dopamine terminals, modulating dopamine release may partly underlie its putative antiaddictive properties.