implications for the long-lasting actions of the anti-addiction drug, Ibogaine.

HSLotsof at aol.com HSLotsof at aol.com
Mon Oct 9 23:31:02 EDT 2006


This may be an important new paper providing information on why ibogaine 
effects are long lasting.

Howard


FASEB J. 2006 Oct 3; [Epub ahead of print]
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Autoregulation of glial cell line-derived neurotrophic factor expression: 
implications for the long-lasting actions of the anti-addiction drug, Ibogaine.
     •     He DY, Ron D.
*Ernest Gallo Research Center,Department of Neurology, University of 
California, San Francisco, Emeryville, California, USA.
We recently showed that the up-regulation of the glial cell line-derived 
neurotrophic factor (GDNF) pathway in the midbrain, is the molecular mechanism by 
which the putative anti-addiction drug Ibogaine mediates its desirable action 
of reducing alcohol consumption (1). Human reports and studies in rodents have 
shown that a single administration of Ibogaine results in a long-lasting 
reduction of drug craving (humans) and drug and alcohol intake (rodents). Here we 
determine whether, and how, Ibogaine exerts its long-lasting actions on GDNF 
expression and signaling. Using the dopaminergic-like SHSY5Y cell line as a 
culture model, we observed that short-term Ibogaine exposure results in a 
sustained increase in GDNF expression that is mediated via the induction of a 
long-lasting autoregulatory cycle by which GDNF positively regulates its own 
expression. We show that the initial exposure of cells to Ibogaine or GDNF results in 
an increase in GDNF mRNA, leading to protein expression and to the 
corresponding activation of the GDNF signaling pathway. This, in turn, leads to a further 
increase in the mRNA level of the growth factor. The identification of a 
GDNF-mediated, autoregulatory long-lasting feedback loop could have important 
implications for GDNF's potential value as a treatment for addiction and 
neurodegenerative diseases.--He, D.-Y., Ron, D. Autoregulation of glial cell 
line-derived neurotrophic factor expression: implications for the long-lasting actions 
of the anti-addiction drug, Ibogaine.
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