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A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats
journal contribution
posted on 2020-05-18, 14:38 authored by Paola Rodrı́guez, Jessika Urbanavicius, José Pedro Prieto, Sara Fabius, Ana Laura Reyes, Vaclav Havel, Dalibor Sames, Cecilia Scorza, Ignacio CarreraAnecdotal reports
and open-label case studies in humans indicated
that the psychedelic alkaloid ibogaine exerts profound antiaddictive
effects. Ample preclinical evidence demonstrated the efficacy of ibogaine,
and its main metabolite, noribogaine, in substance-use-disorder rodent
models. In contrast to addiction research, depression-relevant effects
of ibogaine or noribogaine in rodents have not been previously examined.
We have recently reported that the acute ibogaine administration induced
a long-term increase of brain-derived neurotrophic factor mRNA levels
in the rat prefrontal cortex, which led us to hypothesize that ibogaine
may elicit antidepressant-like effects in rats. Accordingly, we characterized
behavioral effects (dose- and time-dependence) induced by the acute
ibogaine and noribogaine administration in rats using the forced swim
test (FST, 20 and 40 mg/kg i.p., single injection for each dose).
We also examined the correlation between plasma and brain concentrations
of ibogaine and noribogaine and the elicited behavioral response.
We found that ibogaine and noribogaine induced a dose- and time-dependent
antidepressant-like effect without significant changes of animal locomotor
activity. Noribogaine’s FST effect was short-lived (30 min)
and correlated with high brain concentrations (estimated >8 μM
of free drug), while the ibogaine’s antidepressant-like effect
was significant at 3 h. At this time point, both ibogaine and noribogaine
were present in rat brain at concentrations that cannot produce the
same behavioral outcome on their own (ibogaine ∼0.5 μM,
noribogaine ∼2.5 μM). Our data suggests a polypharmacological
mechanism underpinning the antidepressant-like effects of ibogaine
and noribogaine.
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Keywords
time-dependent antidepressant-like effectMetabolite Noribogaine Inducesantidepressant-like effectsbrain concentrationsFSTanimal locomotor activitypolypharmacological mechanism underpinningopen-label case studiesAtypical Psychedelic Ibogainerat prefrontal cortexbrain-derived neurotrophic factor mRNA levelsnoribogainesubstance-use-disorder rodent modelsRats Anecdotal reportspsychedelic alkaloid ibogaine
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