Thursday, June 12, 2008

A cure of alcholism (in rats)

There is a fascinating article about a promising looking new treatment for alcoholism in the latest edition of PNAS. Sebastien Carnicella and colleagues demonstrate in their paper, "GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse", that administering glial cell line-derived neurotrophic factor (a kind of protein) to the ventral tegmental area (part of the reward circuit) of rats rapidly eliminates alcoholism. Interestingly, after multiple injections of GDNF over a couple of weeks, the rats didn't relapse, even when alcohol was freely available. Promising as this looks, it is important to be careful about extrapolating from animal models to humans: many promising treatments fail to transition from basic science to clinical application.

The abstract:
Previously, we demonstrated that the action of the natural alkaloid, ibogaine, to reduce alcohol (ethanol) consumption is mediated by the glial cell line-derived neurotrophic factor (GDNF) in the ventral tegmental area (VTA). Here we set out to test the actions of GDNF in the VTA on ethanol-drinking behaviors. We found that GDNF infusion very rapidly and dose-dependently reduced rat ethanol, but not sucrose, operant self-administration. A GDNF-mediated decrease in ethanol consumption was also observed in rats with a history of high voluntary ethanol intake. We found that the action of GDNF on ethanol consumption was specific to the VTA as infusion of the growth factor into the neighboring substantia nigra did not affect operant responses for ethanol. We further show that intra-VTA GDNF administration rapidly activated the MAPK signaling pathway in the VTA and that inhibition of the MAPK pathway in the VTA blocked the reduction of ethanol self-administration by GDNF. Importantly, we demonstrate that GDNF infused into the VTA alters rats' responses in a model of relapse. Specifically, GDNF application blocked reacquisition of ethanol self-administration after extinction. Together, these results suggest that GDNF, via activation of the MAPK pathway, is a fast-acting selective agent to reduce the motivation to consume and seek alcohol.

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