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 Andrew J, Liang Jian-Hui
Acta Pharmacol Sin. 2014 Jul;35(7):853-61. doi: 10.1038/aps.2014.28. Epub 2014 Jun 9.
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.
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.
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.
BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.
从马钱子种子中提取的马钱子碱（BRU）是甘氨酸受体拮抗剂。我们假设BRU可能通过作用于甘氨酸受体来改变酒精摄入量，并在酒精滥用大鼠模型中评估了BRU的药效学特征和不良反应。
给嗜酒的淡黄头罩大鼠（FH/Wjd）注射BRU（10、20或30mg/kg，皮下注射）。在乙醇双瓶选择饮水范式、乙醇/蔗糖操作性自我给药范式和5天乙醇剥夺试验中检测BRU对酒精摄入量的影响。此外，采用旷场试验评估FH/Wjd大鼠的一般运动活动，并进行条件性位置偏爱（CPP）试验以评估条件性强化作用。
在乙醇双瓶选择饮水范式中，连续10天给予BRU可剂量依赖性地降低乙醇摄入量，同时水摄入量代偿性增加，但每日总液体摄入量和体重未改变。在乙醇/蔗糖操作性自我给药范式中，每次测试前给予BRU（30mg/kg）可显著减少乙醇的杠杆按压次数和乙醇摄入量，而不影响蔗糖（10%）反应次数、总蔗糖摄入量和水的杠杆按压次数。急性给予BRU（30mg/kg）可完全抑制剥夺诱导的乙醇摄入量升高。给予BRU（10、20和30mg/kg）对FH/Wjd大鼠的运动无影响，也未产生位置偏爱或厌恶。
BRU可选择性降低乙醇摄入量，且不良反应最小。因此，BRU可能代表一种治疗酒精中毒的新药物疗法。
