title: Rat strain differences in brain structure and neurochemistry in response to binge alcohol.
abstract: BACKGROUND
  Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)).
  
  
  OBJECTIVE
  Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment.
  
  
  METHODS
  The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain.
  
  
  RESULTS
  As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats.
  
  
  CONCLUSIONS
  The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.
authors.affiliation: Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA, nzahr@stanford.edu.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Zahr
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: Torsten
authors.initials: T
authors.lastname: Rohlfing
authors.forename: Oliver
authors.initials: O
authors.lastname: Hsu
authors.forename: Shara
authors.initials: S
authors.lastname: Vinco
authors.forename: Juan
authors.initials: J
authors.lastname: Orduna
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D063425:Binge Drinking / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D059906:Neuroimaging; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D001224:Aspartic Acid; D000431:Ethanol; C000179:N-acetylaspartate
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