Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 2012 Sep;223(1):55-66. doi: 10.1007/s00213-012-2688-y. Epub 2012 Mar 27.
Understanding naltrexone's effect on motivation to drink and pattern of drinking is important for better treatment outcomes and for comparison with novel medications.
Naltrexone's effects on number and pattern of seeking, self-administration, and extinction responses were evaluated in two groups of baboons trained under a three-component chained schedule of reinforcement (CSR).
Alcohol (4 % w/v; n = 4; alcohol group) or a preferred nonalcoholic beverage (n = 4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2 provided indices of motivation to drink (seeking). Naltrexone (0.32-3.2 mg/kg) and saline were administered before drinking and component 2 extinction sessions.
Acute doses of naltrexone significantly decreased total self-administration responses (p < 0.01), intake volume (p < 0.001), and grams per kilogram of alcohol (p < 0.01) in the alcohol group only. Pattern of drinking did not change, but the number of drinks during the initial drinking bout was decreased significantly by naltrexone for both groups (p < 0.05). During within-session extinction tests, acute naltrexone significantly decreased time to reach extinction (p < 0.01) and number of seeking responses (p < 0.05), particularly early in the extinction period in the alcohol group only. When administered chronically, naltrexone did not decrease progressive ratio breaking points to gain access to alcohol, but dose dependently reduced alcohol self-administration (p < 0.05) by decreasing the magnitude of the initial drinking bout.
The results support clinical observations that naltrexone may be most effective at reducing self-administration in the context of ongoing alcohol availability and may reduce motivation to drink in the presence of alcohol-related cues.
了解纳曲酮对饮酒动机和饮酒模式的影响，对于改善治疗效果以及与新型药物进行比较非常重要。
在两组接受三成分连锁式强化程序（CSR）训练的狒狒中，评估纳曲酮对觅酒、自我给药和消退反应的数量和模式的影响。
仅在 CSR 的第 3 成分中提供酒精（4%w/v；n=4；酒精组）或首选非酒精饮料（n=4；对照组）供自我给药。CSR 的第 2 成分中的反应提供了饮酒动机的指标（觅酒）。在饮酒和第 2 成分消退期间，给予纳曲酮（0.32-3.2mg/kg）和盐水。
急性纳曲酮剂量显著降低了酒精组的总自我给药反应（p<0.01）、摄入量（p<0.001）和每公斤酒精量（p<0.01）。饮酒模式没有改变，但纳曲酮显著减少了两组的初始饮酒回合中的饮酒量（p<0.05）。在单次会话消退测试中，急性纳曲酮显著降低了达到消退的时间（p<0.01）和觅酒反应的数量（p<0.05），仅在酒精组的消退早期如此。慢性给予纳曲酮时，不会降低获得酒精的递增比率突破点，但剂量依赖性地减少了酒精自我给药（p<0.05），减少了初始饮酒回合的幅度。
结果支持临床观察，即纳曲酮在持续提供酒精的情况下，可能最有效地减少自我给药，并且在存在与酒精相关的线索时可能会降低饮酒动机。
