Ethanol induces long-term facilitation of NR2B-NMDA receptor activity in the dorsal striatum: implications for alcohol drinking behavior. Academic Article uri icon

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.

published proceedings

  • J Neurosci

altmetric score

  • 1

author list (cited authors)

  • Wang, J., Carnicella, S., Phamluong, K., Jeanblanc, J., Ronesi, J. A., Chaudhri, N., ... Ron, D.

citation count

  • 146

complete list of authors

  • Wang, Jun||Carnicella, Sebastien||Phamluong, Khanhky||Jeanblanc, Jerome||Ronesi, Jennifer A||Chaudhri, Nadia||Janak, Patricia H||Lovinger, David M||Ron, Dorit

publication date

  • March 2007