Schedule-induced alcohol drinking: non-selective effects of acamprosate and naltrexone
Schedule-induced alcohol drinking: non-selective effects of acamprosate and naltrexone
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DOI：
10.1111/j.1369-1600.2006.00004.x
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发表时间：
2006-03-01
影响因子：
3.4
通讯作者：
Mittleman, Guy
中科院分区：
文献类型：
--
作者：
Escher, Tobie;Mittleman, Guy
阿坎普罗酸和纳曲酮是促进酒精依赖患者戒酒和防止饮酒复发的有效治疗药物，并在动物中剂量依赖性地减少酒精自我给药。本实验的目的是研究阿坎普罗酸和纳曲酮对小鼠饮酒诱发的计划性多饮（SIP）任务的行为特异性。被剥夺食物的雄性C57BL/6J （B6）小鼠被分为三组，分别被分配到5%酒精SIP，水SIP或1小时限制进入调节饮水任务。腹腔注射急性（0、50、100、200、400 mg/kg）和慢性（2 × 100 mg/kg， 10天）阿坎普罗酸或纳曲酮（0、1.0、2.5、5.0 mg/kg）。通过比较SIP患者酒精或水摄入量的变化与有限途径饮酒的变化来确定行为药物特异性。此外，还比较了药物对SIP期间饮酒特异性指标（g/kg消耗量和舔舐效率）与非饮酒指标（食物头部入口和运动活动）的影响。与生理盐水注射相比，急性阿坎普罗酸（400 mg/kg）减少了SIP和调节饮酒条件下的酒精和水的饮用，但对非饮酒措施没有显著影响。长期服用阿坎普罗酸减少了SIP期间的酒精和水饮用，但对调节饮酒或非饮酒措施没有显著影响。纳曲酮（1.0、2.5和5.0 mg/kg）在两种情况下都减少了酒精和水的摄入量，在最高剂量下，显著减少了头部食物摄入量。这些结果表明阿坎普罗酸（急性和慢性）和纳曲酮对酒精自我给药的影响相对非选择性。
Acamprosate and naltrexone are therapeutically effective drugs that promote abstinence and prevent drinking relapse among alcohol-dependent patients, and dose-dependently decrease alcohol self-administration in animals. The purpose of this experiment was to investigate the behavioral specificity of acamprosate and naltrexone treatment in mice on alcohol drinking elicited in a schedule-induced polydipsia (SIP) task. Food-deprived male C57BL/6J (B6) mice were divided into three groups assigned to a 5% alcohol SIP, water SIP, or a 1-hour limited access regulatory water drinking task. Injections (intraperitoneal) of acute (0, 50, 100, 200, 400 mg/kg) and chronic (2 x 100 mg/kg, 10 days) acamprosate, or naltrexone (0, 1.0, 2.5, 5.0 mg/kg) were administered. Behavioral drug specificity was determined by comparing alterations in alcohol or water consumption in SIP with alterations in limited access drinking. Additionally, drug effects on drinking-specific measures (g/kg consumption and lick efficiency) were compared with those of non-drinking measures (head entries for food and locomotor activity) during SIP. In comparison with saline injections, acute acamprosate (400 mg/kg) reduced both alcohol and water drinking in both SIP and the regulatory drinking conditions, but had no significant effects on non-drinking measures. Chronic administration of acamprosate reduced both alcohol and water drinking during SIP, but did not significantly affect regulatory drinking or non-drinking measures. Naltrexone (1.0, 2.5, 5.0 mg/kg) reduced alcohol and water drinking in both paradigms, and at the highest dose, significantly reduced head entries for food. These results indicate that acamprosate (acute and chronic) and naltrexone are relatively non-selective in their effects on alcohol self-administration in this task.