Sirt1 signaling pathway in amygdala regulates heroin addiction behavior in rats
10.3760/cma.j.issn.1006-7884.2019.04.006
- VernacularTitle:大鼠杏仁核内Sirt1信号通路调控海洛因成瘾行为
- Author:
Qian ZHANG
1
;
Yunpeng WANG
;
Xiaohong LU
;
Wei DANG
Author Information
1. 宁夏医科大学基础医学院生物化学与分子生物学系,银川,750001
- Publication Type:Journal Article
- Keywords:
Heroin;
Amygdala;
Conditional place preference;
Sirt;
Histone acetylation
- From:
Chinese Journal of Psychiatry
2019;52(4):267-274
- CountryChina
- Language:Chinese
-
Abstract:
Objective The expression of Sirt family in amygdala was analyzed by heroin conditioned place preference (CPP) in rat model of chronic heroin administration.The target molecule with significant expression change after heroin administration was screened.The expression of target molecule,Sirt1,in amygdala was then interfered to study its regulationon heroin addiction behavior and the downstream molecules.Methods The rats in chronic heroin group were injected intraperitoneally (i.p.)with 5 mg/kg heroin for 7 days.The expression of Sirt family was detected by RT-PCR and Western blot.Quantitative chromatin immunoprecipitation (ChIP) was used to detect the △FosB-regulated Sirt1 expression.Lentivirus-mediated overexpression and inhibitor were used to upregulate/downregulate the expression of Sirt1 in amygdala.The changes of CPP behavior and BDNF expression in heroin-treated rats were observed.Results After chronic heroin administration,the expression of Sirt1 in amygdala was significantly higher than that in saline control group (t14=8.127,P＜0.01).The expression of Sirt1 was increased 6 h after heroin injection (t14=4.997,P＜0.05),24 h (t14=9.711,P＜0.01),3 d (t14=5.407,P＜0.05).After 24 h of the final heroin injection,Sirt1 (t14=5.016,P＜0.01) and acetylated histone H3K9 (t14=2.416,P＜0.05) in amygdala were significantly higher than those in saline control group.△FosB binding to the promoter region of Sirt1 increased significantly (t14=7.301,P＜0.01).Sina1 overexpression (OE-Sirt1) in the amygdala did not affect the natural preference of rats,but the CPP scores of OE-Sirt1 +heroin group in test 2 were significantly higher than those of OE-Sirt1 +saline group (t20=6.629,P＜0.01);there was no difference of the CPP scores between EX527+heroin group and EX527+saline group from test 1 to test 4.The expression of BDNF in OE-Sirt1 + heroin group and OE-Sirt1+saline group was (1.67+0.32) times and (2.66+0.34) times of that in GFP+saline group,respectively.There was no difference of the BDNF expression between EX527 + heroin group and EX527+saline group.Conclusion Heroin may regulate the expression of Sirt1 by up-regulating △FosB in amygdala,and alter the acetylation level of neuronal chromatin histone,resulting in the expression of downstream genes such as BDNF,and ultimately the change in heroin addiction behavior.
