Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration

Authors: Carnicella, Sebastien; He, Dao-Yao1; Yowell, Quinn V.1; Glick, Stanley D2; Ron, Dorit

Source: Addiction Biology, Volume 15, Number 4, October 2010 , pp. 424-433(10)

Publisher: Wiley-Blackwell

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Abstract:

ABSTRACT

Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action.

Keywords: 18-Methoxycoronaridine; GDNF; addiction; ethanol self-administration; ibogaine; noribogaine

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1369-1600.2010.00251.x

Affiliations: 1: The Ernest Gallo Research Center, Emeryville, CA, USA 2: Center of Neuropharmacology and Neuroscience, Albany Medical College

Publication date: October 1, 2010

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