NMDA受体在慢性吗啡处理大鼠伏隔核神经元突触可塑性改变中的作用

Influence of N-methyl-D-aspartic acid receptor on the plasticity of nucleus accumbens synapses in chronic morphine dependent rats

目的:探讨N-甲基-D-天冬氨酸(N-methyl-D-asparticacid,NMDA)受体在慢性吗啡处理大鼠伏隔核神经元突触可塑性中的作用。方法:将15只雄性Sprague-Dawley大鼠随机等分为吗啡组(腹腔注射吗啡,起始剂量5mg/kg,2次/d,逐日递增5mg,至第10天为50mg/kg)、干预组(每次注射吗啡前30min腹腔注射NMDA受体拮抗剂地卓西平0.075mg/kg)及对照组(注射同体积的生理盐水)。末次注射后6d处死取伏隔核并制作电镜标本,日立H-600透射电镜下测量神经元突触界面结构参数。结果:吗啡组大鼠伏隔核神经元突触活性区长度犤(226.46±21.10)nm犦及突触后致密物厚度犤(43.50±5.44)nm犦显著小于对照组犤(319.30±13.40)nm,(58.70±4.95)nm犦(F=49.528,6.725;P均<0.01);干预组大鼠突触后致密物厚度犤(57.30±1.02)nm犦显著大于吗啡组犤(43.50±5.44)nm犦(P<0.05),与对照组差异无显著性。结论:NMDA受体在慢性吗啡处理所导致的伏隔核神经元突触可塑性改变中有重要作用。

AIM:To explore the role of N-methyl-D-aspartic acid(NMDA) receptor in the s ynaptic plasticity induced by chronic morphine treatment in the rat nucleus accu mbens(NAc). METHODS:Fifteen male Sprague-Dawley rats were averagely randomized into morph ine group(intraperitoneal injection of morphine with an initial dosage of 5 mg/k g,twice a day,5 mg increased progressively every day until 50 mg/kg on the 10th day),intervention group(intraperitoneal injection of NMDA receptor antagonist,di zocilpine 0.075 mg/kg,30 minutes before the injection of morphine) and control g roup(intraperitoneal injection of the same volume of saline).After the rats were killed on the 6th day following the last injection, NAc were taken and prepared for electron microscope specimen,and the synaptic interface structural paramete rs were measured under Hitachi H-600 transmission electron microscopy. RESULTS:The length of synaptic active zone[(226.46±21.10)nm]and the thicknes s of post synaptic dense material[(43.50±5.44) nm]in the NAc neurons of morphin e-treated rats were significantly lower than those of the controls respectively [(319.30±13.40) nm,(58.70±4.95) nm](F=49.528,6.725,P< 0.01).The thickness of p ost synaptic dense material of the intervention group was(57.30±1.02) nm,signif icantly thicker than that of the morphine group[(43.50±5.44 ) nm](P< 0.05).But there was no significant difference between the intervention and control groups. CONCLUSION:The NMDA receptor plays an important role in the synaptic plasticit y of NAc neurons induced by chronic morphine treatment.