Reduced effect of NMDA glutamate receptor antagonist on ethanol-induced ataxia and striatal glutamate levels in mice lacking ENT1. Neurosci Lett 2010 Aug 02;479(3):277-81
Date
06/24/2010Pubmed ID
20570605Pubmed Central ID
PMC2913865DOI
10.1016/j.neulet.2010.05.079Scopus ID
2-s2.0-77954141736 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Nam HW, Lee MR, Hinton DJ, Choi DSAuthor
Ryan M. Lee MD Instructor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
2-Amino-5-phosphonovalerateAnimals
Ataxia
Corpus Striatum
Equilibrative Nucleoside Transporter 1
Ethanol
Glutamic Acid
Male
Mice
Mice, Knockout
Receptors, N-Methyl-D-Aspartate