Low-dose prazosin alone and in combination with propranolol or naltrexone: effects on ethanol and sucrose seeking and self-administration in the P rat

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• 作者：Terril L. Verplaetse ; Cristine L. Czachowski
• 关键词：Noradrenergic ; Ethanol ; Combination pharmacotherapy ; Prazosin ; P rat ; Propranolol ; Naltrexone ; Alcohol ; Self ; administration
• 刊名：Psychopharmacology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：232
• 期：15
• 页码：2647-2657
• 全文大小：944 KB
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• 作者单位：Terril L. Verplaetse (1)
  Cristine L. Czachowski (2)
  
  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
  2. Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Psychiatry
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-2072

文摘

Rationale Evidence suggests that the noradrenergic system mediates ethanol reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. Methods This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer seeking and self-administration. Male alcohol-preferring (P) rats (n--0/experiment) were trained to complete a response requirement (RR) resulting in access to 1?% sucrose (n--0) or 10?% ethanol (n--0) for 20?min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, and 1.0?mg/kg, intraperitoneally (IP)), or prazosin in combination with propranolol (5?mg/kg (IP); Exp. 1) or in combination with naltrexone (0.03?mg/kg, subcutaneously (SC); Exp. 2). Results For Exp. 1, prazosin alone effectively decreased sucrose seeking more than ethanol seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol seeking more than sucrose seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp. 2, prazosin alone and naltrexone alone were effective in decreasing ethanol seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol seeking and consumption and sucrose intake, but not sucrose seeking. Conclusions Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone and also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers.