title: Ataxia and c-Fos expression in mice drinking ethanol in a limited access session.
abstract: BACKGROUND
  Although previous murine studies have demonstrated ethanol self-administration resulting in blood ethanol concentrations (BECs) believed to be pharmacologically relevant, to our knowledge, no study reported to date has demonstrated intoxication via ataxia after self-administration. Thus, the goal of this study was to demonstrate ataxia and to examine changes in c-Fos expression in mice after self-administration of intoxicating doses of ethanol.
  
  
  METHODS
  Male C57BL/6J mice were trained to drink a 10% ethanol solution during daily 30-min limited access sessions. Mice were exposed to increasing concentrations of ethanol until a 10% ethanol solution was reached. BEC and ataxia, measured as foot slips off of a balance beam, were examined after the limited access self-administration session. In a separate experiment, various brain structures from mice drinking water or ethanol were examined for changes in c-Fos expression two hr after the limited access session.
  
  
  RESULTS
  Mice drank between 1.5 and 2 g/kg of 10% ethanol during the daily 30-min session. BECs for these mice 15 min after the limited access session ranged between 0.52 and 2.13 mg/ml. A significant increase in foot slips off a balance beam was seen immediately after ethanol consumption during the limited access session. Among mice drinking ethanol, an increase in c-Fos expression was seen in the Edinger-Westphal nucleus, and a decrease in c-Fos expression was seen in the cingulate cortex, ventral tegmental area, lateral and medial septum, CA1 region of the hippocampus, and basolateral amygdala.
  
  
  CONCLUSIONS
  After this procedure in mice, BECs are achieved that are in a range considered pharmacologically relevant and intoxicating. Significant ataxia was observed after ethanol self-administration. Brain regions showing changes in c-Fos expression after voluntary intoxication were similar to those previously reported, suggesting that these brain regions are involved in regulating behavioral effects of alcohol intoxication.
authors.affiliation: Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97239, USA. sharpea@ohsu.edu
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Sharpe
authors.forename: Natalia O
authors.initials: NO
authors.lastname: Tsivkovskaia
authors.forename: Andrey E
authors.initials: AE
authors.lastname: Ryabinin
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D000435:Alcoholic Intoxication / Q000235:genetics*; D000818:Animals; D001259:Ataxia / Q000235:genetics*; D001921:Brain / Q000187:drug effects; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000502:physiology; D016762:Genes, fos / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009048:Motor Skills / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects
chemical_list: D000431:Ethanol