title: Prazosin + Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in P Rats with a Protracted History of Extensive Voluntary Alcohol Drinking, Dependence, and Multiple Withdrawals.
abstract: BACKGROUND
  Prazosin (PRZ; an α1 -adrenergic receptor antagonist) and naltrexone (NTX; a nonspecific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively bred for high voluntary alcohol drinking (alcohol-preferring or "P"), and the combination of PRZ + NTX decreases alcohol drinking more effectively than does either drug alone. As drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence, and repeated withdrawals closely resembling human alcoholism.
  
  
  METHODS
  Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/d access to food, water, and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: (i) daily alcohol access with daily drug treatment, (ii) intermittent alcohol access with daily drug treatment, (iii) intermittent alcohol access with occasional drug treatment, and (iv) postdeprivation reinstatement of alcohol access.
  
  
  RESULTS
  The combination of PRZ + NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ + NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects, or malaise.
  
  
  CONCLUSIONS
  Both daily and "as-needed" treatment with PRZ + NTX are highly effective in suppressing daily, intermittent, and postdeprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence, and repeated relapse, as commonly encountered in clinical practice.
authors.affiliation: VISN 20 Mental Illness Research, Education and Clinical Center, Seattle, Washington.|VA Puget Sound Health Care System, Seattle, Washington.|Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Rasmussen
authors.affiliation: VA Puget Sound Health Care System, Seattle, Washington.|Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Kincaid
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Janice C
authors.initials: JC
authors.lastname: Froehlich
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000437:Alcoholism / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D004359:Drug Therapy, Combination; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D011224:Prazosin / Q000008:administration & dosage*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D009292:Narcotic Antagonists; D009271:Naltrexone; D011224:Prazosin
keywords: Alcohol; Alcoholism Treatment; Naltrexone; Noradrenergic; Opioid; Prazosin