title: Withdrawal severity after chronic intermittent ethanol in inbred mouse strains.
abstract: BACKGROUND
  To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling-induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens.
  
  
  METHODS
  Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced.
  
  
  RESULTS
  Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 +/- 0.02 mg/ml and we restricted the range of this value to 1.00-2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, low dose (1.29 +/- 0.1 mg/ml) and high dose (1.71 +/- 0.02 mg/ml). After the third inhalation exposure, ethanol-exposed and air-exposed groups were tested hourly for handling-induced convulsions for 10 hour and at hour 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups.
  
  
  CONCLUSIONS
  The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the high-dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hours) ethanol withdrawal studies, supporting the influence of common genes on all three responses.
authors.affiliation: Department of Veterans Affairs and Department of Behavioral Neuroscience, Portland Alcohol Research Center, Oregon Health & Science University, Portland, Oregon 97239, USA. mettenp@ohsu.edu
authors.forename: Pamela
authors.initials: P
authors.lastname: Metten
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Sorensen
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Cameron
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Yu
authors.forename: John C
authors.initials: JC
authors.lastname: Crabbe
mesh_terms: D020270:Alcohol Withdrawal Seizures / Q000097:blood / Q000235:genetics*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D013045:Species Specificity
chemical_list: D000431:Ethanol