EVIDENCE THAT IBOGAINE RELEASES DOPAMINE FROM THE CYTOPLASMIC POOL INISOLATED MOUSE STRIATUM

We measured the effect of ibogaine on the tritium efflux from isolated mouse striatum preloaded with [H-3]dopamine ([H-3]DA). Ibogaine incre ased the basal tritium outflow in a concentration-dependent manner, bu t it was without effect on electrical stimulation-induced tritium over flow. Separation of the released radioactivity after ibogaine administ ration showed that this drug increased the release of [H-3]DA and [H-3 ]-dihydroxyphenylacetic acid ([H-3]DOPAC), but the efflux of O-methyla ted-deaminated metabolites was not changed. The dopamine (DA)-releasin g effect of ibogaine was reduced by the DA uptake inhibitors cocaine a nd nomifensine. The tritium efflux evoked by ibogaine was not altered by omission of Ca2+ from the perfusion buffer or by inhibition of the voltage-sensitive Na+ channels with tetrodotoxin. Ibogaine maintained its effect on release from superfused striatum prepared from reserpine -pretreated mice. The ibogaine-induced tritium release measured from m ouse striatum that was preloaded with [H-3]DA was not affected by the D-2 DA receptor ligands (-)-quinpirole and (+/-)-sulpiride, indicating that the ibogaine-induced release is not subject to presynaptic autor eceptor regulation. Ibogaine failed to affect [H-3]DA uptake and reten tion in mouse striatum. These data indicate that at the nerve terminal level ibogaine releases DA, and the primary source for the release is probably the cytoplasmic pool. The DA-releasing effect of ibogaine ma y have importance in mediation of its hallucinogenic action, as seen i n a frequent practice in African cults.