King Courtney E, Griffin William C, Luderman Lauryn N, Kates Malcolm M, McGinty Jacqueline F, Becker Howard C
Charleston Alcohol Research Center, Departments of Psychiatry and Neuroscience, Medical University of South Carolina & VAMC, Charleston, South Carolina.
Alcohol Clin Exp Res. 2017 May;41(5):955-964. doi: 10.1111/acer.13359. Epub 2017 Mar 27.
Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption.
Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge-like drinking ("drinking in the dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive-ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models.
Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose.
These results indicate that oxytocin reduces EtOH consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.
过量饮酒仍然是一个重要的健康问题，且缺乏有效的治疗方法。中枢催产素系统已成为酒精和药物成瘾潜在的重要治疗靶点。这些研究检验了催产素可减少酒精摄入的假设。
使用类似暴饮暴食的饮酒模型（“黑暗中饮酒”）让雄性C57BL/6J小鼠接触酒精（20% v/v），该模型还包括使用舔舐计数器电路来评估摄入的时间模式以及在笼内进行两瓶选择饮酒实验。此外，还评估了在固定比率和累进比率时间表下酒精（12% v/v）和蔗糖（5% w/v）的自我给药情况。在这些模型中测试了广泛的全身给药催产素剂量（0至10 mg/kg）。
在暴饮暴食饮酒模型中，催产素（0、0.3、1、3或10 mg/kg）剂量依赖性地减少酒精摄入（最大减少45%），较低有效剂量对一般运动活动影响最小。催产素受体拮抗剂预处理可阻断催产素的作用，且在酒精瓶处的接触（舔舐）模式表明饮用酒精的动机降低。催产素减少了两瓶选择饮酒量，而不改变总体液体摄入量。催产素还以剂量相关的方式减少了对酒精和蔗糖的操作性反应。然而，催产素在不改变对蔗糖反应的剂量下降低了对酒精的反应和动机（断点值）。
这些结果表明，催产素在不同的自我给药模型中可减少酒精摄入。这些作用不太可能是由于该神经肽的一般镇静作用。此外，催产素在不改变对天然奖励（蔗糖）反应的剂量下降低了对酒精的动机。虽然一些证据支持催产素受体在介导这些作用中发挥作用，但还需要进一步研究以阐明潜在机制。尽管如此，这些结果支持了催产素作为酒精使用障碍治疗方法的治疗潜力。
