Excessive alcohol consumption is blocked by glial cell line-derived neurotrophic factor
Excessive alcohol consumption is blocked by glial cell line-derived neurotrophic factor
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DOI：
10.1016/j.alcohol.2008.12.001
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发表时间：
2009-02-01
期刊：
影响因子：
2.3
通讯作者：
Ron, Dorit
中科院分区：
文献类型：
--
作者：
Camicella, Sebastien;Amamoto, Ryoji;Ron, Dorit
我们之前发现，在大鼠操作性自我给药范例中，腹侧被盖区（VTA）中胶质细胞系源性神经营养因子（GDNF）途径的激活可减少适量酒精（乙醇）的摄入量。在此，我们着手评估 VTA 中的 GDNF 对过量自愿乙醇消费的影响。 Long-Evans 大鼠被训练以间歇性两瓶选择饮用模式饮用大量 20% 乙醇溶液。每周对大鼠进行 3 次 24 小时训练，当大鼠达到 5.5 g/kg/24 小时的乙醇消耗基线时，测量 GDNF 的作用。我们发现，在饮酒开始前 10 分钟将 GDNF 微量注射到 VTA 中，可显着降低乙醇摄入量和偏好，但不会影响总液体摄入量。我们进一步表明，GDNF 极大地减少了训练开始时的第一轮过量乙醇摄入，以及后来在暗循环期间发生的完成活动。这些数据表明，GDNF 是一种快速且持久的“暴饮暴食”乙醇消耗抑制剂。 (C) 2009 Elsevier Inc. 保留所有权利。
We previously found that activation of the glial cell line-derived neurotrophic factor (GDNF) pathway in the ventral tegmental area (VTA) reduces moderate alcohol (ethanol) intake in a rat operant self-administration paradigm. Here, we set out to assess the effect of GDNF in the VTA on excessive voluntary consumption of ethanol. Long-Evans rats were trained to drink large quantities of a 20% ethanol solution in an intermittent-access two-bottle choice drinking paradigm. The rats were given three 24-h sessions per week, and GDNF's actions were measured when rats achieved a baseline of ethanol consumption of 5.5 g/kg/24 h. We found that microinjection of GDNF into the VTA 10 min before the beginning of an ethanol-drinking session significantly reduced ethanol intake and preference, but did not affect total fluid intake. We further show that GDNF greatly decreased both the first bout of excessive ethanol intake at the beginning of the session, and the later consummatory activity occurring during the dark cycle. These data suggest that GDNF is a rapid and long-lasting inhibitor of "binge-like" ethanol consumption. (C) 2009 Elsevier Inc. All rights reserved.