The [alpha]1-Adrenergic Receptor Antagonist, Doxazosin, Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats

• Published in: Alcoholism, clinical and experimental research Vol. 37; no. 2; p. 202
• Main Authors: O'Neil, Meghan L, Beckwith, Lauren E, Kincaid, Carrie L, Rasmussen, Dennis D
• Format: Journal Article
• Language: English
• Published: Austin Wiley Subscription Services, Inc 01-02-2013
• Subjects: Alcohol use; Rodents
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2012.01884.x

Background Evidence supports a role for the noradrenergic system in alcohol drinking in animals and humans. Our previous studies demonstrated the efficacy of prazosin, an [alpha]1-adrenergic antagonist, in decreasing alcohol drinking in rat models of alcohol dependence. Prazosin has also been shown to decrease alcohol drinking in treatment-seeking alcohol-dependent men. Clinically, the use of prazosin is limited by the requirement for multiple daily administrations, whereas doxazosin, a structurally similar [alpha]1-adrenergic antagonist, requires only once-daily dosing. In this study, we tested the hypothesis that doxazosin, like prazosin, would decrease alcohol drinking in rats selectively bred for alcohol preference (P line). Methods Adult male P rats were given 2 h/d scheduled access to a 2-bottle choice (15% v/v alcohol vs. water) session 5 d/wk (M-F), with food and water available ad libitum 24 h/d. Rats were injected with doxazosin (0 to 10 mg/kg, IP) 40 minutes prior to initiation of the alcohol access session in 3 trials (of 3, 5, and 5 consecutive days) each separated by 5 to 8 weeks. The third trial included 1 day without alcohol access (for locomotor testing), and 1 day of a single hour of alcohol access (for plasma alcohol determination). Results Doxazosin significantly reduced alcohol intake in all 3 trials. The 5 mg/kg dose consistently reduced alcohol intake, increased water drinking, did not affect locomotor activity, and resulted in lower plasma alcohol concentrations, suggesting that the doxazosin-induced reduction in alcohol drinking was not dependent on a motor impairment or an alteration in alcohol clearance. Conclusions Doxazosin decreases voluntary alcohol consumption by male alcohol-preferring (P) rats, supporting a role for the noradrenergic system in alcohol drinking in P rats and suggesting that doxazosin could potentially be an effective once-daily pharmacotherapeutic agent for the treatment of alcohol use disorders. [PUBLICATION ABSTRACT]