Combining the α1-adrenergic receptor antagonist, prazosin, with the β-adrenergic receptor antagonist, propranolol, reduces alcohol drinking more effectively than either drug alone

Dennis D. Rasmussen, Lauren E. Beckwith, Carrie L. Kincaid, Janice Froehlich

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1532-1539
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Adrenergic Antagonists
Prazosin
Propranolol
Alcohol Drinking
Alcohols
Pharmaceutical Preparations
Rats
Adrenergic Receptors
Drug Combinations
Chemical activation
Recurrence
Food
Water
Animals

Keywords

  • Alcoholism Treatment
  • Noradrenergic
  • Prazosin
  • Propranolol

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology
  • Medicine(all)

Cite this

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title = "Combining the α1-adrenergic receptor antagonist, prazosin, with the β-adrenergic receptor antagonist, propranolol, reduces alcohol drinking more effectively than either drug alone",
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.",
keywords = "Alcoholism Treatment, Noradrenergic, Prazosin, Propranolol",
author = "Rasmussen, {Dennis D.} and Beckwith, {Lauren E.} and Kincaid, {Carrie L.} and Janice Froehlich",
year = "2014",
doi = "10.1111/acer.12441",
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pages = "1532--1539",
journal = "Alcoholism: Clinical and Experimental Research",
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T1 - Combining the α1-adrenergic receptor antagonist, prazosin, with the β-adrenergic receptor antagonist, propranolol, reduces alcohol drinking more effectively than either drug alone

AU - Rasmussen, Dennis D.

AU - Beckwith, Lauren E.

AU - Kincaid, Carrie L.

AU - Froehlich, Janice

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Alcoholism Treatment

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