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Wednesday, July 8, 2009

Binge Drinking Upregulates Accumbens mGluR5–Homer2–PI3K Signaling: Functional Implications for Alcoholism
The Journal of Neuroscience, July 8, 2009, 29(27):8655-8668

The glutamate receptor-associated protein Homer2 regulates alcohol-induced neuroplasticity within the nucleus accumbens (NAC), but the precise intracellular signaling cascades involved are not known. This study examined the role for NAC metabotropic glutamate receptor (mGluR)–Homer2–phosphatidylinositol 3-kinase (PI3K) signaling in regulating excessive alcohol consumption within the context of the scheduled high alcohol consumption (SHAC) model of binge alcohol drinking.

Consistent with the hypothesis that mGluR5–Homer–PI3K signaling may be a mechanism governing excessive alcohol intake, the "anti-binge" effects of MPEP and wortmannin were not additive, nor were they observed in the mGluR5F1128R transgenic mice. Finally, mice genetically selected for a high versus low SHAC phenotype differed in NAC mGluR, Homer2, and PI3K activity, consistent with the hypothesis that augmented NAC mGluR5–Homer2–PI3K signaling predisposes a high binge alcohol-drinking phenotype.

Together, these data point to an important role for NAC mGluR5–Homer2–PI3K signaling in regulating binge-like alcohol consumption that has relevance for our understanding of the neurobiology of alcoholism and its pharmacotherapy.


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