Effect of ibogaine on serotonergic and dopaminergic interactions in striatum from mice and rats

The effect of ibogaine (Endabuse, NIH 10567) on serotonin uptake and release, and on serotonergic modulation of dopamine release, was measured in striatal tissue from rats and mice. Two hours after treatment in vivo with ibogaine (40 mg/kg i.p.) the uptake of labeled [3H]serotonin and [3H]dopamine uptake in striatal tissue was similar in the ibogaine-treated animal to that in the control. The 5HT1B agonist CGS-12066A (10(-5) M) had no effect on stimulation-evoked tritium release from mouse or rat striatal tissue preloaded with [3H]serotonin; however, it elevated tritium efflux from striatal tissue preloaded with [3H]dopamine. This increase was not seen in mice treated with ibogaine 2 or 18 hours previously, or in rats treated 2 hours before. Dopamine autoreceptor responses were not affected by ibogaine pretreatment in either mouse or rat striatal tissue; sulpiride increased stimulation-evoked release of tritium from tissue preloaded with [3H]dopamine. The long-lasting effect of ibogaine on serotonergic functioning, in particular, its blocking of the 5HT1B agonist-mediated increase in dopamine efflux, may have significance in the mediation of its anti-addictive properties.