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Patricia H. Janak

2 papers in the library · 313 citations · publishing 2005-2008

Papers

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

Journal of Neuroscience January 19, 2005 Dao‐yao He, Nancy N. H. Mcgough, Ajay Ravindranathan et al. 181 citations

Ibogaine, a natural alkaloid with side effects that prevent clinical use, reduces alcohol consumption in rats. In two-bottle choice and operant self-administration tests, ibogaine decreased ethanol intake and also reduced relapse-like drinking. The effect is mediated by glial cell line-derived neurotrophic factor (GDNF) in the ventral tegmental area (VTA): ibogaine microinjected into the VTA reduced self-administration, systemic ibogaine increased GDNF expression in the midbrain, and in dopaminergic SHSY5Y cells ibogaine activated the GDNF pathway (phosphorylation of Ret and ERK1). Intra-VTA GDNF mimicked ibogaine's effect, while anti-GDNF antibodies blocked it. GDNF in the VTA therefore mediates ibogaine's action on ethanol consumption, suggesting GDNF as a target for alcoholism medications that could avoid ibogaine's side effects.

DOI: 10.1523/jneurosci.3959-04.2005 (opens in new tab) Full text (opens in new tab) Ventral tegmental area Neurotrophic factors Pharmacology Self-administration +6

GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse.

Proceedings of the National Academy of Sciences of the United States of America June 10, 2008 Sebastien Carnicella, Viktor Kharazia, Jérôme Jeanblanc et al. 132 citations

Infusing GDNF directly into the ventral tegmental area (VTA) of rats rapidly and dose-dependently reduces their operant self-administration of alcohol, but not sucrose. This effect is specific to the VTA, as infusion into the neighboring substantia nigra does not alter alcohol responding. GDNF activates the MAPK signaling pathway in the VTA, and blocking this pathway prevents the reduction in alcohol self-administration. GDNF also blocks the reacquisition of alcohol self-administration after extinction, indicating it reduces relapse-like behavior. The findings suggest GDNF, via MAPK activation, acts as a fast-acting and selective agent to diminish alcohol consumption and seeking.

DOI: 10.1073/pnas.0711755105 (opens in new tab) Full text (opens in new tab) Alcoholism treatment Gdnf Addiction neuroscience Pharmacotherapy