Alcohol-sensitive type 1 equilibrative nucleotide transporter (ENT1) is known to regulate glutamate signaling in the striatum as well as ethanol intoxication. However, it was unclear whether altered extracellular glutamate levels in ENT1(-/-) mice contribute to ethanol-induced behavioral changes. Here we report that altered glutamate signaling in ENT1(-/-) mice is implicated in the ethanol-induced locomotion and ataxia by NMDA receptor antagonist, CGP37849. ENT1(-/-) mice appear less intoxicated following sequential treatment with CGP37849 and ethanol, compared to ENT1(+/+) littermates on the rotarod. These results indicate that inhibiting NMDA glutamate receptors is critical to regulate the response and susceptibility of alcohol related behaviors. Interestingly, a microdialysis experiment showed that the ventral striatum of ENT1(-/-) mice is less sensitive to the glutamate-reducing effect of the NMDA receptor antagonist compared to the dorsal striatum. Our findings suggest that differential glutamate neurotransmission in the striatum regulates ethanol intoxication.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913865 | PMC |
| http://dx.doi.org/10.1016/j.neulet.2010.05.079 | DOI Listing |
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