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, Jerome 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.