The α1‐Adrenergic Receptor Antagonist, Prazosin, Reduces Alcohol Drinking in Alcohol‐Preferring (P) Rats

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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 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.