Evidence that ibogaine releases dopamine from the cytoplasmic pool in isolated mouse striatum.
We measured the effect of ibogaine on the tritium efflux from isolated mouse striatum preloaded with [3H]dopamine ([3H]DA). Ibogaine increased the basal tritium outflow in a concentration-dependent manner, but it was without effect on electrical stimulation-induced tritium overflow. Separation of the released radioactivity after ibogaine administration showed that this drug increased the release of [3H]DA and [3H]-dihydroxyphenylacetic acid ([3H]DOPAC), but the efflux of O-methylated-deaminated metabolites was not changed. The dopamine (DA)-releasing effect of ibogaine was reduced by the DA uptake inhibitors cocaine and 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 mouse striatum that was preloaded with [3H]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 autoreceptor regulation. Ibogaine failed to affect [3H]DA uptake and retention 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 may have importance in mediation of its hallucinogenic action, as seen in a frequent practice in African cults.
Harsing
L G
LG
Center for Neurochemistry, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY.
Sershen
H
H
Lajtha
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D007050:Ibogaine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D015222:Sodium Channels; D015102:3,4-Dihydroxyphenylacetic Acid; D007050:Ibogaine; D004298:Dopamine