Reduced effect of NMDA glutamate receptor antagonist on ethanol-induced ataxia and striatal glutamate levels in mice lacking ENT1

NEUROSCIENCE LETTERS

卷:479

Article

Nam, Hyung Wook¹  Lee, Moonnoh R.¹  Hinton, David J.¹  Choi, Doo-Sup^1,2,3 

[1] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA

[2] Mayo Clin, Coll Med, Dept Psychiat & Psychol, Rochester, MN 55905 USA

[3] Mayo Clin, Coll Med, Mol Neurosci Program, Rochester, MN 55905 USA

关键词: Alcoholism;    ENT1;    Glutamate neurotransmission;    CGP37849;    Microdialysis;    Ataxia;    Caudate-putamen;    Nucleus accumbens;   

DOI  :  10.1016/j.neulet.2010.05.079

来源: Elsevier

【 摘 要 】

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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free