Li Yixin, Xia Baijuan, Li Rongrong, Yin Dan, Liang Wenmei
Department of Histology and Embryology, Guizhou Medical University, Guiyang, Guizhou, China (mainland).
Med Sci Monit. 2017 Jun 9;23:2805-2815. doi: 10.12659/msm.904670.
BACKGROUND The aim of this study was to explore how changes in the expression of BDNF in MLDS change the effect of BDNF on dopamine (DA) neurons, which may have therapeutic implications for heroin addiction. MATERIAL AND METHODS We established a rat model of heroin addiction and observed changes in the expression of BDNF, DA, dopamine receptor (DRD), dopamine transporter (DAT), and other relevant pathways in NAc. We also assessed the effect of BDNF overexpression in the NAc, behavioral changes of heroin-conditioned place preference (CPP), and naloxone withdrawal in rats with high levels of BDNF. We established 5 adult male rat groups: heroin addiction, lentivirus transfection, blank virus, sham operation, and control. The PCR gene chip was used to study gene expression changes. BDNF lentivirus transfection was used for BDNF overexpression. A heroin CPP model and a naloxone withdrawal model of rats were established. RESULTS Expression changes were found in 20 of the 84 DA-associated genes in the NAc of heroin-addicted rats. Weight loss and withdrawal symptoms in the lentivirus group for naloxone withdrawal was less than in the blank virus and the sham operation group. These 2 latter groups also showed significant behavioral changes, but such changes were not observed in the BDNF lentivirus group before or after training. DRD3 and DAT increased in the NAc of the lentivirus group. CONCLUSIONS BDNF and DA in the NAc are involved in heroin addiction. BDNF overexpression in NAc reduces withdrawal symptoms and craving behavior for medicine induced by environmental cues for heroin-addicted rats. BDNF participates in the regulation of the dopamine system by acting on DRD3 and DAT.
背景 本研究的目的是探讨中脑边缘多巴胺系统(MLDS)中脑源性神经营养因子(BDNF)表达的变化如何改变BDNF对多巴胺(DA)神经元的作用,这可能对海洛因成瘾具有治疗意义。
材料与方法 我们建立了海洛因成瘾大鼠模型,并观察了伏隔核(NAc)中BDNF、DA、多巴胺受体(DRD)、多巴胺转运体(DAT)及其他相关通路表达的变化。我们还评估了NAc中BDNF过表达的效果、海洛因条件性位置偏爱(CPP)的行为变化以及BDNF水平高的大鼠的纳洛酮戒断情况。我们建立了5组成年雄性大鼠组:海洛因成瘾组、慢病毒转染组、空白病毒组、假手术组和对照组。使用PCR基因芯片研究基因表达变化。采用BDNF慢病毒转染进行BDNF过表达。建立了大鼠海洛因CPP模型和纳洛酮戒断模型。
结果 在海洛因成瘾大鼠的NAc中,84个与DA相关的基因中有20个出现表达变化。纳洛酮戒断时,慢病毒组的体重减轻和戒断症状比空白病毒组和假手术组轻。后两组也表现出明显的行为变化,但在训练前后的BDNF慢病毒组中未观察到此类变化。慢病毒组NAc中的DRD3和DAT增加。
结论 NAc中的BDNF和DA参与海洛因成瘾。NAc中BDNF过表达可减轻海洛因成瘾大鼠由环境线索诱导的药物戒断症状和渴求行为。BDNF通过作用于DRD3和DAT参与多巴胺系统的调节。