海洛因依赖大鼠VTA区NMDA受体介导的多巴胺神经元膜电流的变化

Change of dopaminergic neurons' membrane currents mediated by NMDA receptor in the VTA regions of heroin addiction rat

目的:探讨海洛因依赖大鼠中脑腹侧被盖区(vental tegmental area,VTA)NMDA受体介导的多巴胺(DA)神经元膜电流的变化。方法:20只SD雄性大鼠随机分成对照组、海洛因依赖组(以下称依赖组)。按剂量递增原则皮下注射给予海洛因,纳络酮催促戒断,确定海洛因依赖模型的建立。免疫组织化学方法标记VTA区DA神经元酪氨酸羟化酶(tyrosine hydroxylase,TH),脑片膜片钳技术记录其NMDA受体特异性激动剂N-methyl-D-aspartate(NMDA)介导的膜电流。结果:建立的海洛因依赖模型组大鼠催促戒断症状的评分符合成瘾模型评分标准;海洛因依赖组VTA区DA神经元TH表达上调(P<0.05);海洛因依赖组VTA区NMDA受体介导的DA神经元膜电流减小(P<0.05)。结论:海洛因依赖组VTA区DA神经元TH反应增强,神经元的兴奋性受到抑制。

Objective： To investigate the change of dopaminergic neurons＇ membrane currents mediated by NMDA re- ceptor in the ventral tegmental area （VTA） regions of heroin addiction rat. Methods： 20 male Sprague-Dawley rats were randomly divided into control group and heroin-addicted group. Heroin-addicted rats were chronically treated by subcuta- neous injection of heroin according to the principle of daily increasing dose. Rats＇ withdrawal symptoms were induced by naloxone in order to confirm heroin-addicted model was established. Tyrosine hydroxylase （TH）- staining was used to mark the dopamine neurons in the VTA regions. Brain slice patch-clamp technique was used to re- cord the variety of dopamine neurons＇ membrane current mediated by NMDA agonist. Results： The withdrawal symptoms of heroin-addicted rats were scored and results according with the heroin-addicted model score standard. TH-immunoreac- tive of DA neurons in the VTA regions was up-regulated in heroin-addicted group （ P 〈 0.05 ）. The DA neurons mem- brane current mediated by NMDA receptor was decreased in the VTA regions of heroin-addicted group （P 〈 0.05 ）. Conclusion： The immunoreactive of TH in the VTA regions was increased in heroin-addicted group, and the excitability of DA neurons was inhibited.