PT - JOURNAL ARTICLE AU - Jun Wang AU - Sebastien Carnicella AU - Khanhky Phamluong AU - Jerome Jeanblanc AU - Jennifer A. Ronesi AU - Nadia Chaudhri AU - Patricia H. Janak AU - David M. Lovinger AU - Dorit Ron TI - Ethanol Induces Long-Term Facilitation of NR2B-NMDA Receptor Activity in the Dorsal Striatum: Implications for Alcohol Drinking Behavior AID - 10.1523/JNEUROSCI.4749-06.2007 DP - 2007 Mar 28 TA - The Journal of Neuroscience PG - 3593--3602 VI - 27 IP - 13 4099 - http://www.jneurosci.org/content/27/13/3593.short 4100 - http://www.jneurosci.org/content/27/13/3593.full SO - J. Neurosci.2007 Mar 28; 27 AB - Addiction is characterized by compulsive alcohol or drug taking and seeking, and the dorsal striatum has been implicated in such maladaptive persistent habits. The NMDA receptor (NMDAR), which is a major target of alcohol, is implicated in striatal-based habit learning. We found that, in the dorsal striatum, alcohol (ethanol) exposure produced an increase in the phosphorylation of the NR2B subunit of the NMDAR, and a corresponding increase in the activity of Fyn kinase, which phosphorylates NR2B. We further observed an ethanol-mediated long-term facilitation (LTF) of the activity of NR2B-containing NMDARs (NR2B-NMDARs) in the dorsal striatum. This LTF is Fyn kinase dependent, because it was observed in Fyn wild-type but not in Fyn knock-out mice. Importantly, none of these biochemical and physiological changes was observed in the ventral striatum. Finally, dorsal but not ventral striatum infusion of a Fyn or NR2B-NMDAR inhibitor reduced rat operant self-administration of ethanol. Our results suggest that the Fyn-mediated phosphorylation and LTF of NR2B-NMDAR activity in the dorsal striatum after exposure to ethanol may underlie aberrant plasticity that contributes to mechanisms underlying alcohol drinking behavior.