title: Effects of the glucocorticoid antagonist, mifepristone, on the consequences of withdrawal from long term alcohol consumption.
abstract: BACKGROUND
  Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice.
  
  
  METHODS
  The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining.
  
  
  RESULTS
  Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment.
  
  
  CONCLUSIONS
  The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits.
authors.affiliation: Department of Basic Medical Sciences, St George's, University of London, Cranmer Terrace, London, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Jacquot
authors.forename: Adam P
authors.initials: AP
authors.lastname: Croft
authors.forename: Mark A
authors.initials: MA
authors.lastname: Prendergast
authors.forename: Patrick
authors.initials: P
authors.lastname: Mulholland
authors.forename: Sidney G
authors.initials: SG
authors.lastname: Shaw
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Little
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000188:drug therapy*; D000818:Animals; D005938:Glucocorticoids / Q000032:analysis / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy / Q000523:psychology; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000188:drug therapy* / Q000523:psychology
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone