title: Exploring the role of central astrocytic glutamate uptake in ethanol reward in mice.
abstract: BACKGROUND
  Alcoholism is associated with specific brain abnormalities revealed through postmortem studies, including a reduction in glial cell number and dysregulated glutamatergic neurotransmission. Whether these abnormalities contribute to the etiology of alcoholism, are consequences of alcohol use, or both is still unknown.
  
  
  METHODS
  We investigated the role of astrocytic glutamate uptake in ethanol (EtOH) binge drinking in mice, using the "drinking in the dark" (DID) paradigm by blocking the astrocytic glutamate transporter (GLT-1) with intracerebroventricular (ICV) administration of dihydrokainic acid (DHK). To determine whether astrocytic glutamate uptake regulates the conditioned rewarding effects of EtOH, we examined the effects of ICV DHK on the acquisition and expression of EtOH-induced conditioned place preference.
  
  
  RESULTS
  Blocking central astrocytic glutamate uptake selectively attenuated EtOH binge drinking behavior in mice. DHK did not alter the acquisition or expression of preference for EtOH-associated cues, indicating that reduced astrocytic glutamate trafficking may decrease binge-like drinking without altering the conditioned rewarding effects of EtOH.
  
  
  CONCLUSIONS
  Several alternative conclusions are plausible, however, interpreting these data in the context of the human literature, these findings suggest that the reduction of glia in the alcoholic brain may not be a predisposing factor to developing alcoholism and could be a consequence of EtOH toxicity that decreases excessive EtOH intake.
authors.affiliation: Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts; Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Smith
authors.forename: Catherine S
authors.initials: CS
authors.lastname: John
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Sypek
authors.forename: Dost
authors.initials: D
authors.lastname: Ongür
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Barry
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Bechtholt
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism* / Q000502:physiology; D057967:Infusions, Intraventricular; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012201:Reward
chemical_list: D027322:Amino Acid Transport System X-AG; D000431:Ethanol; D018698:Glutamic Acid; C020889:dihydrokainic acid; D007608:Kainic Acid
keywords: Astrocyte; Drinking in the Dark; Ethanol; Glutamate; Place Preference