title: Altered glutamatergic neurotransmission in the striatum regulates ethanol sensitivity and intake in mice lacking ENT1.
abstract: Alcohol-sensitive type 1 equilibrative nucleoside transporter (ENT1) regulates adenosine-mediated glutamate neurotransmission in the brain. Our behavioral studies suggest that the diminished aversive effects of ethanol and the increased resistance to acute ethanol intoxication in mice lacking ENT1, could be related to increased voluntary ethanol self-seeking behavior. In addition, we found that ENT1 null mice were resistant to the ataxic effects of glutamate antagonists when tested on a rotarod. Using microdialysis experiments, we examined glutamate levels in the dorsal and ventral striatum in response to ethanol. In the dorsal striatum of ENT1 null mice, a low intoxicating dose of ethanol (1.5 g/kg) induced a greater increase of glutamate levels, while a higher hypnotic dose of ethanol (3.0 g/kg) decreased to a lesser degree the glutamate levels, compared with that of wild-type mice. In the ventral striatum, however, the low (1.5 g/kg) and the high (3.0 g/kg) ethanol doses altered glutamate levels similarly in both genotypes. Our results suggest that adenosine-regulated glutamatergic signaling contributes to a reduced level of alcohol response, which might be associated with a higher susceptibility for alcoholism in humans.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Jihuan
authors.initials: J
authors.lastname: Chen
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: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Taehyun
authors.initials: T
authors.lastname: Kim
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kawamura
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Janak
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003216:Conditioning, Operant / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry / Q000379:methods; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000502:physiology; D012646:Self Administration / Q000379:methods
chemical_list: D002492:Central Nervous System Depressants; D033721:Equilibrative Nucleoside Transporter 1; D018691:Excitatory Amino Acid Antagonists; C498476:SLC29A1 protein, mouse; D000431:Ethanol; D018698:Glutamic Acid; D016291:Dizocilpine Maleate