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.
Brain research bulletin – January 01, 1995
Source: PubMed
Summary
Ibogaine shows promise in disrupting stimulant drug dependency by modulating key neurotransmitter systems. In experiments with mice, ibogaine pretreatment (40 mg/kg) eliminated the inhibitory effect of the kappa-opioid agonist U 62066 on dopamine release. Additionally, while a 10(-6) M dose of phenylbiguanide reduced stimulation-evoked dopamine release, a higher dose increased it. Notably, ibogaine did not alter the effects of cocaine on dopamine release. These findings suggest that ibogaine's interaction with specific receptors may contribute to its potential antiaddictive effects.
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.