Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 13, Pages 3593-3602Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4749-06.2007
Keywords
accumbens; addiction; drinking; Fyn; NMDA receptors; self-administration; striatum; synaptic plasticity
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Funding
- Intramural NIH HHS Funding Source: Medline
- NIAAA NIH HHS [R01AA/MH13438-01A1] Funding Source: Medline
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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.
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