Escher Tobie, Mittleman Guy
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, CA 92037, USA.
Addict Biol. 2006 Mar;11(1):55-63. doi: 10.1111/j.1369-1600.2006.00004.x.
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.
阿坎酸和纳曲酮是治疗有效的药物，可促进酒精依赖患者戒酒并防止饮酒复发，且能剂量依赖性地减少动物的酒精自我给药。本实验的目的是研究阿坎酸和纳曲酮治疗对小鼠在定时诱导多饮（SIP）任务中引发的酒精饮用行为的特异性。将食物剥夺的雄性C57BL/6J（B6）小鼠分为三组，分别进行5%酒精SIP、水SIP或1小时有限制饮水调节任务。腹腔注射急性（0、50、100、200、400mg/kg）和慢性（2×100mg/kg，10天）阿坎酸或纳曲酮（0、1.0、2.5、5.0mg/kg）。通过比较SIP中酒精或水消耗量的变化与有限制饮水变化来确定行为药物特异性。此外，在SIP期间，将药物对饮酒特定指标（g/kg消耗量和舔舐效率）的影响与非饮酒指标（获取食物的头部探入次数和运动活动）进行比较。与注射生理盐水相比，急性阿坎酸（400mg/kg）在SIP和调节饮水条件下均减少了酒精和水的饮用，但对非饮酒指标无显著影响。慢性给予阿坎酸可减少SIP期间的酒精和水饮用，但对调节饮水或非饮酒指标无显著影响。纳曲酮（1.0、2.5、5.0mg/kg）在两种范式中均减少了酒精和水的饮用，且在最高剂量时显著减少了获取食物的头部探入次数。这些结果表明，在该任务中，阿坎酸（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。
