GDNF anybody??

HSLotsof at aol.com HSLotsof at aol.com
Wed Jan 19 15:55:24 EST 2005


Where the author gets the idea that ibogaine is not used clinically because 
of side effects is a mystery but it sounds good if you have an alternate 
product in mind.  I guess 18-mc and noribogaine get cut out of the loop too.

Howard

http://www.jneurosci.org/cgi/content/abstract/25/3/619

Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of 
the Anti-Addiction Drug Ibogaine against Alcohol Consumption 

Dao-Yao He,1 * Nancy N. H. McGough,1 * Ajay Ravindranathan,1 Jerome Jeanblanc,
1 Marian L. Logrip,1,3 Khanhky Phamluong,1 Patricia H. Janak,1,2,3 and Dorit 
Ron1,2,3 

1Ernest Gallo Research Center, 2Department of Neurology, 3Neuroscience 
Graduate Program, University of California, San Francisco, Emeryville, California 
94608 


Alcohol addiction manifests as uncontrolled drinking despite negative 
consequences. Few medications are available to treat the disorder. Anecdotal reports 
suggest that ibogaine, a natural alkaloid, reverses behaviors associated with 
addiction including alcoholism; however, because of side effects, ibogaine is 
not used clinically. In this study, we first characterized the actions of 
ibogaine on ethanol self-administration in rodents. Ibogaine decreased ethanol 
intake by rats in two-bottle choice and operant self-administration paradigms. 
Ibogaine also reduced operant self-administration of ethanol in a relapse model. 
Next, we identified a molecular mechanism that mediates the desirable 
activities of ibogaine on ethanol intake. Microinjection of ibogaine into the ventral 
tegmental area (VTA), but not the substantia nigra, reduced 
self-administration of ethanol, and systemic administration of ibogaine increased the expression
 of glial cell line-derived neurotrophic factor (GDNF) in a midbrain region 
that includes the VTA. In dopaminergic neuron-like SHSY5Y cells, ibogaine 
treatment upregulated the GDNF pathway as indicated by increases in phosphorylation 
of the GDNF receptor, Ret, and the downstream kinase, ERK1 (extracellular 
signal-regulated kinase 1). Finally, the ibogaine-mediated decrease in ethanol 
self-administration was mimicked by intra-VTA microinjection of GDNF and was 
reduced by intra-VTA delivery of anti-GDNF neutralizing antibodies. Together, 
these results suggest that GDNF in the VTA mediates the action of ibogaine on 
ethanol consumption. These findings highlight the importance of GDNF as a new 
target for drug development for alcoholism that may mimic the effect of ibogaine 
against alcohol consumption but avoid the negative side effects. 



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