The alpha1-adrenergic receptor antagonist, prazosin, reduces alcohol drinking in alcohol-preferring (P) rats.
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.
Rasmussen
Dennis D
DD
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.
Alexander
Laura L
LL
Raskind
Murray A
MA
Froehlich
Janice C
JC
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011224:Prazosin