4-PBA对吗啡诱导小鼠CPP的影响  

The effects of 4-PBA on morphine-induced CPP in mice

作　　者：殷剑敏 韩卫 张明照[2,3,4] 王志荣 刘鑫鑫 左雨蒙 阎亭羽 刘新社 李涛 YIN Jian-min;HAN Wei;ZHANG Ming-zhao;WANG Zhi-rong;LIU Xin-xin;ZUO Yu-meng;YAN Ting-yu;LIU Xin-she;LI Tao(Fenyang College of Shanxi Medical University,Lvliang 032200,Shanxi,China;College of Forensic Medicine,Xi'an Jiaotong University Health Science Center,Xi'an 710061,China;Institute of Forensic Injury,Institute of Biological Evidence,Xi'an Jiaotong University,Xi'an 710061,China;The Key Laboratory of Health Ministry for Forensic Science,Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]山西医科大学汾阳学院,山西吕梁032200 [2]西安交通大学医学部法医学院,西安710061 [3]西安交通大学生物证据研究院,法医损伤研究所,西安710061 [4]西安交通大学卫健委法医学重点实验室,西安710061

出　　处：《中国药物依赖性杂志》2024年第4期299-306,共8页Chinese Journal of Drug Dependence

基　　金：国家自然科学基金(82072112)。

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。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 of PFC,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 

分 类 号：R749[医药卫生—神经病学与精神病学]