李晓丹,油珅,罗素兰,等.α-芋螺毒素TxIB抗药物依赖的初步探索[J].中国海洋药物,2020,39(6):39-44. |
α-芋螺毒素TxIB抗药物依赖的初步探索 |
Preliminary Study on the Anti-Addiction Effect of α-Conotoxin TxIB |
投稿时间:2020-04-20 修订日期:2020-06-30 |
DOI: |
中文关键词: α-芋螺毒素TxIB 成瘾 条件性位置偏爱 |
English Keywords:α-conotoxin TxIB addiction conditioned place preference (CPP) |
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中文摘要: |
目的 探究作用于α6/α3β2β3烟碱型乙酰胆碱受体(nAChRs)的α-芋螺毒素TxIB对吗啡/尼古丁诱导条件性位置偏爱(CPP)的影响,为进一步设计筛选抗药物依赖的芋螺毒素提供理论和实验依据。方法 选用SPF级雄性C57BL/6小鼠,采用皮下注射吗啡(5 mg/kg)或尼古丁(0.5 mg/kg)建立CPP模型。侧脑室注射不同剂量的α-芋螺毒素TxIB,记录小鼠在伴药箱的停留时间。结果 皮下注射吗啡(5 mg/kg)或尼古丁(0.5 mg/kg)均可成功建立CPP模型,经侧脑室注射不同剂量的TxIB后测值,发现TxIB能显著性抑制吗啡/尼古丁诱导小鼠CPP的表达(P<0.05),且存在剂量依赖性效果。侧脑室注射最高剂量TxIB(10 nmol)对生理盐水对照组小鼠在伴药箱停留时间无影响(P>0.05)。结论 α-芋螺毒素TxIB可以抑制吗啡/尼古丁诱导小鼠CPP的表达,有望进一步开发成为戒烟戒毒的候选新药。 |
English Summary: |
Objective Explore the effects of α-conotoxin TxIB on morphine/nicotine induced conditioned place preference in mice, which is a potent antagonist of α6/α3β2β3 nicotinic acetylcholine receptors (nAChRs). Methods The eligible male C57BL/6 mice were subcutaneous (s.c.) injected with morphine (5 mg/kg) or nicotine (0.5 mg/kg) for conditioned place preference (CPP). Then the different doses of α-conotoxin TxIB were intracerebroventricular (i.c.v.) injected, and the time spent in the drug-paired box was recorded. Results The results indicated that injection of 5 mg/kg morphine(s.c.) or 0.5 mg/kg nicotine(s.c.) can successfully establish CPP models, and injection of α-conotoxin TxIB(i.c.v.) dose-dependently blocked the expression of morphine/nicotine CPP in mice(P<0.05). The highest dose of TxIB (10 nmol) in saline-treated mice in the CPP model to be observed had no statistical differences (P>0.05). Conclusion α-Conotoxin TxIB can inhibit the expression of morphine/nicotine-induced CPP in mice, which is promising for development as anti-addiction drug candidate. |
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