title: Low-dose stimulatory effects of ethanol during adolescence in rat lines selectively bred for high alcohol intake.
abstract: BACKGROUND
  The low-dose stimulatory effect of ethanol (EtOH) in rats has been hypothesized to reflect its hedonic effects and to be associated with a genetic predisposition toward high alcohol preference. To test the hypothesis that phenotypes associated with high alcohol preference in adulthood are also present in adolescent rats at the time of onset of alcohol drinking, the current study examined the effects of EtOH on locomotor activity (LMA) during adolescence in lines of rats selectively bred for divergent alcohol intakes.
  
  
  METHODS
  Subjects were adolescent (31-40 days of age) rats from the alcohol-preferring (P) and -nonpreferring (NP) lines and from the high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) replicate lines. On day 1, all subjects (n = 8-10/line/gender/dose) received intraperitoneal saline injections and were placed in the activity monitor for 30 min. On day 2, subjects received intraperitoneal saline or 0.25, 0.50, 0.75, 1.0, or 1.5 g EtOH/kg.
  
  
  RESULTS
  The LMA of male and female P rats was increased with low doses (0.25-0.75 g/kg) and decreased at the highest dose (1.5 g/kg) of EtOH. Similar effects were observed with low doses of EtOH on the LMA of HAD-1 and HAD-2 rats. None of the EtOH doses stimulated LMA in the NP, LAD-1, or LAD-2 rats, although all of the low-alcohol-intake lines of rats showed decreased LMA at the highest dose of EtOH. Only the P rats among the high-alcohol-consuming lines of rats showed decreased LMA at the highest dose of EtOH.
  
  
  CONCLUSIONS
  Selective breeding for high alcohol consumption seems to be associated with increased sensitivity to the low-dose stimulating effects of EtOH and reduced sensitivity to the high-dose motor-impairing effects of ethanol. The expression of these phenotypes emerges during adolescence by the age of onset of alcohol-drinking behavior.
authors.affiliation: Department of Psychiatry and Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202-4887, USA. zrodd@iupui.edu
authors.forename: Z A
authors.initials: ZA
authors.lastname: Rodd
authors.forename: R L
authors.initials: RL
authors.lastname: Bell
authors.forename: D L
authors.initials: DL
authors.lastname: McKinzie
authors.forename: A A
authors.initials: AA
authors.lastname: Webster
authors.forename: J M
authors.initials: JM
authors.lastname: Murphy
authors.forename: L
authors.initials: L
authors.lastname: Lumeng
authors.forename: T-K
authors.initials: TK
authors.lastname: Li
authors.forename: W J
authors.initials: WJ
authors.lastname: McBride
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001947:Breeding / Q000379:methods; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D000431:Ethanol