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

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.

• Authors: Dennis D Rasmussen, Laura L Alexander, Murray A Raskind, Janice C Froehlich
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 33 Issue 2 Pg. 264-72 (Feb 2009) ISSN: 1530-0277 [Electronic] England
• PMID: 19032582 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-Antagonists
• Prazosin

Topics

• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-Antagonists (pharmacology)
• Alcohol Drinking (genetics, psychology)
• Animals
• Data Interpretation, Statistical
• Dose-Response Relationship, Drug
• Drinking
• Male
• Prazosin (pharmacology)
• Rats