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The α 1 ‐Adrenergic Receptor Antagonist, Prazosin, Reduces Alcohol Drinking in Alcohol‐Preferring (P) Rats
Author(s) -
Rasmussen Dennis D.,
Alexander Laura L.,
Raskind Murray A.,
Froehlich Janice C.
Publication year - 2009
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2008.00829.x
Subject(s) - prazosin , alcohol , antagonist , medicine , endocrinology , adrenergic , ethanol , adrenergic receptor , self administration , receptor , pharmacology , chemistry , biochemistry
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 α 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 α 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.