The effects of ibogaine on dopamine and serotonin transport in rat brain synaptosomes

Ibogaine has been shown to affect biogenic amine levels in selected brain regions. Because of the involvement of these neurotransmitters in drug addiction, the effects of ibogaine on biogenic amine transport may contribute to the potential anti-addictive properties of ibogaine in vivo. With rat brai...

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Bibliographic Details
Published in:Brain research bulletin 1999-04, Vol.48 (6), p.641-647
Main Authors: Wells, Gregg B, Lopez, Melissa C, Tanaka, Jacqueline C
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biological Transport - drug effects
Brain - drug effects
Brain - metabolism
Cerebral Cortex - drug effects
Cerebral Cortex - metabolism
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Dopamine - metabolism
Dopamine release
Dopamine transporter
Dopamine uptake
Drug addictions
Hallucinogens - pharmacology
Ibogaine
Ibogaine - pharmacology
Medical sciences
Potassium - pharmacology
Rats
Rats, Wistar
Serotonin - metabolism
Serotonin transporter
Serotonin uptake
Synaptosomes
Synaptosomes - drug effects
Synaptosomes - metabolism
Toxicology
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Summary:Ibogaine has been shown to affect biogenic amine levels in selected brain regions. Because of the involvement of these neurotransmitters in drug addiction, the effects of ibogaine on biogenic amine transport may contribute to the potential anti-addictive properties of ibogaine in vivo. With rat brain synaptosomes as our experimental system, we measured the effects of ibogaine on the uptake and release of dopamine (DA) and serotonin (5-HT). Ibogaine competitively blocked both DA and 5-HT uptake with IC50 values of 20 μM at 75 nM 3H-DA and 2.6 μM at 10 nM 3H-5-HT. Ibogaine had no effect on K+-induced release of 3H-DA from preloaded synaptosomes, but 20 μM and 50 μM ibogaine inhibited roughly 40% and 60%, respectively, of the K+-induced release of 3H-5-HT from preloaded synaptosomes. In the absence of a depolarizing stimulus, ibogaine evoked a small release of 3H-DA but not 3H-5-HT. These relatively low-potency effects of ibogaine on DA and 5-HT uptake in synaptosomes are consistent with the low binding affinity of ibogaine that has been previously reported for DA and 5-HT transporters. Our results show that if ibogaine modulates DA and 5-HT levels in the brain by directly blocking their uptake, then a concentration of ibogaine in the micromolar range is required. Furthermore, if the anti-addictive effects of ibogaine require this concentration, then ibogaine likely exerts these effects through a combination of neurotransmitter pathways, because binding affinities and functional potencies of ibogaine in the micromolar range have been reported for a variety of neuronal receptors and transporters.
ISSN:0361-9230
1873-2747
DOI:10.1016/S0361-9230(99)00053-2