title: Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal.
abstract: BACKGROUND
  Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals.
  
  
  METHODS
  Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; nondependent control animals received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically.
  
  
  RESULTS
  The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7 to 9 hours and returning to baseline within 24 hours; withdrawal severity was greater in D2 than in B6 mice (experiment 1). Postwithdrawal delays in initial ethanol access (1, 3, or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (experiment 2). The postwithdrawal enhancement of ethanol intake persisted over a 5-day abstinence period in D2 mice (experiment 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than nondependent mice (experiment 4).
  
  
  CONCLUSIONS
  Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism.
authors.affiliation: Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR 97239, USA. cunningh@ohsu.edu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Cunningham
authors.forename: Tara L
authors.initials: TL
authors.lastname: Fidler
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Murphy
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Mulgrew
authors.forename: Phoebe J
authors.initials: PJ
authors.lastname: Smitasin
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012646:Self Administration; D013045:Species Specificity; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000235:genetics; D013997:Time Factors
chemical_list: D000431:Ethanol