title: Ethanol induces long-term facilitation of NR2B-NMDA receptor activity in the dorsal striatum: implications for alcohol drinking behavior.
abstract: 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.
authors: Ernest Gallo Research Center, Emeryville, California 94608, USA.
authors: Jun
authors: J
authors: Wang
authors: Sebastien
authors: S
authors: Carnicella
authors: Khanhky
authors: K
authors: Phamluong
authors: Jerome
authors: J
authors: Jeanblanc
authors: Jennifer A
authors: JA
authors: Ronesi
authors: Nadia
authors: N
authors: Chaudhri
authors: Patricia H
authors: PH
authors: Janak
authors: David M
authors: DM
authors: Lovinger
authors: Dorit
authors: D
authors: Ron
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D003216:Conditioning, Operant; D003342:Corpus Striatum / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D012646:Self Administration; D012932:Social Facilitation
chemical_list: C121001:NR2B NMDA receptor; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn