大鼠基底外侧杏仁核组蛋白乙酰化对吗啡成瘾记忆的调控作用

发布时间：2018-11-12 20:22

【摘要】：为了探索组蛋白乙酰化对吗啡成瘾记忆相关分子表达调控机制,文章选取健康成年雄性SD大鼠34只,随机分为正常对照组(n=6)及基底外侧杏仁核(Basolateral amygdala,BLA)颅内定位手术组(n=28)。在条件性位置偏爱(Conditioned place preference,CPP)训练阶段,大鼠BLA内给予组蛋白去乙酰化酶抑制剂曲古抑菌素A(Trichostafin A,TSA)并且腹腔注射吗啡溶液(10.0 mg/kg),对照组给予相同体积的10%二甲基亚砜(Dimethyl sulfoxide,DMSO)或盐水。应用蛋白质印记方法,检测吗啡诱导大鼠CPP建立后BLA内组蛋白H3K14乙酰化和脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)蛋白表达水平。结果显示,腹腔注射10 mg/kg吗啡能成功建立CPP。吗啡、TSA联合给药组大鼠比单纯吗啡给药组大鼠表现出更强烈的CPP(P0.0001)。吗啡和TSA都能使BLA内的组蛋白H3乙酰化水平和BDNF的表达显著增高(P0.0001),同时二者之间具有协同作用。结果表明,大鼠BLA内组蛋白乙酰化水平与吗啡成瘾记忆形成有关,抑制BLA内组蛋白去乙酰化酶(Histone deacetylases,HDACs)的活性可强化吗啡诱导的线索记忆的形成;大鼠BLA内BDNF参与了吗啡诱导的线索记忆的形成并可能受到组蛋白乙酰化的调控。
[Abstract]:In order to explore the regulation mechanism of histone acetylation on the expression of memory related molecules in morphine addiction, 34 healthy male SD rats were randomly divided into normal control group (nong6) and basal lateral amygdaloid nucleus (Basolateral amygdala,). BLA) Intracranial localization operation group (NM 28). During conditioned place preference (Conditioned place preference,CPP) training stage, rats were given histone deacetylase inhibitor (A (Trichostafin) and intraperitoneal injection of morphine solution (10.0 mg/kg) in BLA. The control group was given the same volume of 10% dimethyl sulfoxide (Dimethyl sulfoxide,DMSO) or saline. The acetylation of histone H3K14 and the expression of brain-derived neurotrophic factor (Brain-derived neurotrophic factor,BDNF) in BLA of morphine induced rat CPP were detected by protein imprinting method. The results showed that CPP. could be successfully established by intraperitoneal injection of morphine for 10 mg/kg. The CPP of morphine, TSA combined administration group was stronger than that of morphine alone group (P0.0001). Both morphine and TSA could significantly increase the level of histone H 3 acetylation and the expression of BDNF in BLA (P0.0001), and there was a synergistic effect between them. The results showed that the level of histone acetylation in rat BLA was related to the formation of morphine addictive memory. Inhibiting the activity of histone deacetylase (Histone deacetylases,HDACs) in BLA could enhance the formation of morphine induced clue memory. BDNF in rat BLA is involved in the formation of clue memory induced by morphine and may be regulated by histone acetylation.
【作者单位】：西安交通大学法医学院;
【基金】：国家自然科学基金项目(编号:81172910)资助
【分类号】：R96

【共引文献】