4-PBA对吗啡诱导小鼠CPP的影响
The effects of 4-PBA on morphine-induced CPP in mice
殷剑敏 1韩卫 2张明照 2王志荣 2刘鑫鑫 2左雨蒙 2阎亭羽 2刘新社 2李涛2
作者信息
- 1. 山西医科大学汾阳学院,山西吕梁 032200;西安交通大学医学部法医学院,西安 710061;西安交通大学生物证据研究院,法医损伤研究所,西安 710061;西安交通大学卫健委法医学重点实验室,西安 710061
- 2. 西安交通大学医学部法医学院,西安 710061;西安交通大学生物证据研究院,法医损伤研究所,西安 710061;西安交通大学卫健委法医学重点实验室,西安 710061
- 折叠
摘要
目的 探讨组蛋白去乙酰化酶抑制剂4-PBA对吗啡诱导小鼠条件性位置偏爱(conditioned place preference,CPP)的影响,并研究相关组蛋白乙酰化参与吗啡成瘾的调控机制.方法 研究4-PBA在不同阶段对吗啡诱导CPP的影响,检测小鼠前额叶皮层(prefrontal cortex,PFC)、伏隔核(nucleus accumbens,NAc)、尾状壳核(caudate and putamen,CPu)和海马(hippocampus,Hip)四个脑区H4K5ac和H4K8ac的表达水平变化情况.结果 (1)4-PBA可明显抑制吗啡诱导CPP的形成;10 mg/kg的吗啡反复给药使小鼠NAc脑区中H4K5ac、H4K8ac表达下降.(2)4-PBA对吗啡诱导小鼠CPP的表达无明显影响;10 mg/kg吗啡使小鼠NAc脑区中H4K5ac、H4K8ac表达下降.(3)4-PBA显著促进了吗啡诱导小鼠CPP的消退;CPP消退使小鼠PFC脑区中H4K5ac、H4K8ac表达下降.(4)4-PBA对吗啡诱导小鼠CPP复吸有潜在的抑制作用;吗啡诱导的CPP复吸使小鼠PFC脑区中H4K5ac、H4K8ac表达下降.结论 4-PBA可作为吗啡成瘾的潜在治疗药物;H4K5ac和H4K8ac参与了吗啡成瘾的调控.
Abstract
Objective To investigate the effect of HDAC inhibitor 4-PBA on morphine-induced CPP in mice,and to study the regulation mechanism of histone acetylation involved in morphine addiction.Methods To study the effect of 4-PBA on morphine-induced CPP at different stages,and to detect the expression levels of H4K5ac and H4K8ac in four brain regions ofPFC,NAc,CPu and Hip.Results(1)4-PBA can significantly inhibit the acquisition of morphine-induced CPP;repeated administration of 10 mg/kg morphine decreased the expression of H4K5ac and H4K8ac in the NAc brain region of mice.(2)4-PBA had no significant effect on the expression of CPP in morphine-induced mice;the expression of H4K5ac and H4K8ac in NAc brain area of mice decreased with 10 mg/kg morphine.(3)4-PBA markedly promoted the extinction of morphine-induced CPP in mice;CPP extinction decreased the expression of H4K5ac and H4K8ac in PFC brain region of mice.(4)4-PBA has a potential inhibitory effect on morphine-induced CPP reinstatement in mice;morphine-induced CPP reinstatement reduced H4K5ac and H4K8ac expression in PFC brain region of mice.Conclusion 4-PBA can be used as a potential treatment for morphine addiction.H4K5ac and H4K8ac are involved in the regulation of morphine addiction.
关键词
吗啡/4-苯基丁酸钠/条件性位置偏爱/表观遗传/组蛋白乙酰化Key words
morphine/sodium4-phenylbutyrate/conditional place preference/epigenetic/histone acetylation引用本文复制引用
出版年
2024
NETL
NSTL
万方数据