The alpha1-adrenergic receptor antagonist, prazosin, reduces alcohol drinking in alcohol-preferring (P) rats

  • Alcohol Clin Exp Res. 2009 Feb;33(2):264-72. doi: 10.1111/j.1530-0277.2008.00829.x.
Dennis D Rasmussen  1 ,  Laura L Alexander ,  Murray A Raskind ,  Janice C Froehlich
Affiliations
  • 1. VISN 20 Mental Illness Research Education and Clinical Center, Mental Health Service, Department of Veterans Affairs Medical Center and University of Washington, Seattle, Washington, USA.
PMID: 19032582 DOI: 10.1111/j.1530-0277.2008.00829.x
Abstract

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 alpha(1)-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 alpha(1)-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.

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