title: Reduced effect of NMDA glutamate receptor antagonist on ethanol-induced ataxia and striatal glutamate levels in mice lacking ENT1.
abstract: 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.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Nam
authors.forename: Moonnoh R
authors.initials: MR
authors.lastname: Lee
authors.forename: David J
authors.initials: DJ
authors.lastname: Hinton
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D000431:Ethanol / Q000633:toxicity*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D016194:Receptors, N-Methyl-D-Aspartate; C498476:SLC29A1 protein, mouse; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D000431:Ethanol; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate