The α1-adrenergic receptor antagonist, prazosin, reduces alcohol drinking in alcohol-preferring (P) rats

Dennis D. Rasmussen, Laura L. Alexander, Murray A. Raskind, Janice C. Froehlich

Research output: Contribution to journalArticle

60 Scopus citations


Background: Preliminary evidence suggest that noradrenergic signaling may play a role in mediating alcohol drinking behavior in both humans and rats. Accordingly, we tested the hypothesis that blockade of α1- adrenergic receptors will suppress alcohol drinking in rats selectively bred for alcohol preference (P line). Methods: Adult male P rats were given 24-hour access to food and water and scheduled access to a 15% (v/v) alcohol solution for 2 hours daily. Rats were injected IP with the α1-adrenergic receptor antagonist, prazosin (0, 0.5, 1.0, 1.5, or 2.0 mg/kg body weight), once a day at 15 minutes prior to onset of the daily 2-hour 2-bottle choice, alcohol versus water, access period for 2 consecutive days and then 3 weeks later for 5 consecutive days. Results: Prazosin significantly reduced (p < 0.01) alcohol intake during the initial 2 daily administrations, and this reduction of alcohol intake was maintained for 5 consecutive days by daily prazosin treatment in the subsequent more prolonged trial (p < 0.05). The prazosin-induced reduction of alcohol intake was not dependent upon drug-induced motor impairment since increases in water drinking (p < 0.05) were exhibited during the 2-hour access periods during both 2- and 5-day prazosin treatment. Conclusions: The results indicate that the noradrenergic system plays a role in mediating alcohol drinking in rats of the P line and suggest that prazosin - a safe, well-characterized, and well-tolerated drug - may be an effective pharmacotherapeutic agent for the treatment of alcohol use disorders.

Original languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Issue number2
StatePublished - Feb 2009


  • Alcohol
  • Alcohol-preferring
  • Noradrenergic
  • P rats
  • Prazosin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology
  • Medicine(all)

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