Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. O'Hearn, E. and Molliver, M.E. Neuroscience 55:303-310, 1993.
Abstract: The
indole alkaloids ibogaine and harmaline are beta-carboline derivatives
that cause both hallucinations and tremor. Reports that ibogaine
may have potent anti-addictive properties have led to initiatives
that it be tested for the treatment of opiate and cocaine addiction.
In this study, ibogaine-treated rats were analysed for evidence
of neurotoxic effects because human clinical trials of ibogaine
have been proposed. We recently found that ibogaine induces a
marked glial reaction in the cerebellum with activated astrocytes
and microglia aligned in parasagittal stripes within the vermis.
Based on those findings, the present study was conducted to investigate
whether ibogaine may cause neuronal injury or degeneration. The
results demonstrate that, after treatment with ibogaine or harmaline,
a subset of Purkinje cells in the vermis degenerates. We observed
a loss of the neuronal proteins microtubule-associated protein
2 and calbindin co-extensive with loss of Nissl-stained Purkinje
cell bodies. Argyrophilic staining of Purkinje cell bodies, dendrites
and axons was obtained with the Gallyas reduced silver method
for degenerating neurons. Degenerating neurons were confined to
narrow parasagittal stripes within the vermis. We conclude that
both ibogaine and harmaline have selective neurotoxic effects
which lead to degeneration of Purkinje cells in the cerebellar
vermis. The longitudinal stripes of neuronal damage may be related
to the parasagittal organization of the olivocerebellar climbing
fiber projection. Since these drugs produce sustained activation
of inferior olivary neurons, we hypothesize that release of an
excitatory amino acid from climbing fiber synaptic terminals may
lead to excitotoxic degeneration of Purkinje cells
© 1997The Ibogaine Dossier