Brucine suppresses ethanol intake and preference in alcohol-preferring Fawn-Hooded rats.
Brucine suppresses ethanol intake and preference in alcohol-preferring Fawn-Hooded rats.
复制标题
马钱子碱抑制偏好酒精的小黄帽大鼠的乙醇摄入和偏好。
DOI：
10.1038/aps.2014.28
复制
发表时间：
2014
影响因子：
8.2
通讯作者：
Liang,Jian-Hui
中科院分区：
文献类型：
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作者：
Li,Yu-Ling;Liu,Qing;Gong,Qi;Li,Jun-Xu;Wei,Shou-Peng;Wang,Yan-Ting;Liang,Hui;Zhang,Min;Jing,Li;Yong,Zheng;Lawrence,AndrewJ;Liang,Jian-Hui
目的：从马钱子中提取的马钱子碱(Brucine，Bru)是甘氨酸受体拮抗剂L。我们假设Bru可能通过作用于甘氨酸受体而改变酒精的消耗，并评价Bru在酒精滥用大鼠模型中的药效学特征和不良反应。方法：偏爱酒精(FH/Wjd)大鼠皮下注射Bru(10，20或30 mg/kg，sc)。在酒精2瓶选择饮用范式、乙醇/蔗糖操作者自我给药范式和5-d酒精剥夺实验中考察Bru对酒精摄入量的影响。结果：在酒精2瓶选择饮酒模式中，Bru连续10d剂量依赖性地减少了大鼠的酒精摄入量和代偿性增加的饮水量，但对每日总液体摄入量和体重无明显影响。在乙醇/蔗糖操纵者自我给药范例中，在每次测试前给予Bru(30 mg/kg)显著减少乙醇杠杆按压次数和乙醇摄入量，而不影响蔗糖(10%)应答次数、总蔗糖摄入量和杠杆按压加水次数。Bru(30 mg/kg)的急性处理可完全抑制剥夺所致的乙醇消耗量的增加。Bru(10、20和30 mg/kg)处理不改变FH/Wjd大鼠的运动能力，也不产生位置偏爱或厌恶。结论：Bru选择性地减少酒精摄入量，不良反应最小。因此，Bru可能代表了一种治疗酒精中毒的新药物疗法。
Aim:Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse.Methods:Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect.Results:In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion.Conclusion:BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.