Combining the α1-Adrenergic Receptor Antagonist, Prazosin, with the β-Adrenergic Receptor Antagonist, Propranolol, Reduces Alcohol Drinking More Effectively Than Either Drug Alone

Authors

  • Dennis D. Rasmussen,

    Corresponding author
    1. VISN 20 Mental Illness Research, Education and Clinical Center, Seattle, Washington
    2. VA Puget Sound Health Care System , Seattle, Washington
    3. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington
    • Reprint requests: Dennis D. Rasmussen, PhD, 116 MIRECC, VA Puget Sound Health Care System Medical Center, 1660 S Columbian Way, Seattle, WA 98108; Tel.: 206-277-3370; Fax: 206-768-5456; E-mail: drasmuss@u.washington.edu

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  • Lauren E. Beckwith,

    1. VA Puget Sound Health Care System , Seattle, Washington
    2. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington
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  • Carrie L. Kincaid,

    1. VA Puget Sound Health Care System , Seattle, Washington
    2. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington
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  • Janice C. Froehlich

    1. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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Abstract

Background

Evidence suggests that activation of the noradrenergic system may contribute to alcohol drinking in animals and humans. Our previous studies demonstrated that blocking α1-adrenergic receptors with the antagonist, prazosin, decreased alcohol drinking in rats under various conditions. As noradrenergic activation is also regulated by β-adrenergic receptors, we now examine the effects of the β-adrenergic receptor antagonist, propranolol, alone or in combination with prazosin, on alcohol drinking in rats selectively bred for high voluntary alcohol intake and alcohol preference (P line).

Methods

Two studies were conducted with male P rats. In study 1, rats were allowed to become alcohol-dependent during 14 weeks of ad libitum access to food, water, and 20% alcohol, and the effect of propranolol (5 to 15 mg/kg, intraperitoneally [IP]) and prazosin (1 to 2 mg/kg, IP) on alcohol intake during withdrawal was assessed. In study 2, the effect of propranolol (5 mg/kg, IP) and prazosin (2 mg/kg, IP) on alcohol intake following prolonged imposed abstinence was assessed.

Results

Alcohol drinking following propranolol treatment was variable, but the combination of propranolol + prazosin consistently suppressed alcohol drinking during both alcohol withdrawal and following prolonged imposed abstinence, and the combination of these 2 drugs was more effective than was treatment with either drug alone.

Conclusions

Treatment with prazosin + propranolol, or a combination of other centrally active α1- and β-adrenergic receptor antagonists, may assist in preventing alcohol relapse in some individuals.

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