Shi Xiang-Dang, Wang Gui-Bin, Ma Yao-Ying, Ren Wei, Luo Fei, Cui Cai-Lian, Han Ji-Sheng
Neuroscience Research Institute, Key laboratory for Neuroscience, Peking University, the Ministry of Education, 38 Xueyuan Road, Beijing 100083, PR China.
Brain Res Mol Brain Res. 2004 Nov 4;130(1-2):124-33. doi: 10.1016/j.molbrainres.2004.07.016.
Previous studies have shown that peripheral electrical stimulation (PES) can suppress morphine-induced conditioned place preference (CPP) and the reinstatement of extinguished CPP in the rat. The present study was performed to elucidate if preproenkephalin (PPE) and preprodynorphin (PPD) mRNAs in the nucleus accumbens (NAc) play a role in this event. Rats were trained with morphine for 4 days to establish CPP paradigm. They were then given 15-min test once a day for eight consecutive days for extinction trial. Twenty-four hours after the 8th session of extinction trials, rats were given peripheral electrical stimulation (PES) at 2 or 100 Hz once a day for 3 days, then a morphine-priming injection at a dose of 1, 2, or 4 mg/kg to reinstate the extinguished CPP. At the end of the experiment, PPE and PPD mRNA levels in the nucleus acccumbens (NAc) were determined by the semiquantitative RT-PCR technique. The results showed that PES at 2- and 100-Hz administered 30 min a day for 3 days suppressed both the expression of morphine-induced CPP and the reinstatement of extinguished CPP. PES at 2 Hz increased preproenkephalin (PPE) mRNA levels, whereas PES of 100 Hz that of preprodynorphin (PPD) mRNA levels in the NAc. These findings suggest that enkephalin and dynorphin in NAc may play important roles in the mechanisms underlying the inhibitory effect of PES on the expression and reinstatement of morphine-induced CPP in rats.
以往研究表明，外周电刺激（PES）可抑制大鼠吗啡诱导的条件性位置偏爱（CPP）以及消退后CPP的恢复。本研究旨在阐明伏隔核（NAc）中前脑啡肽原（PPE）和前强啡肽原（PPD）mRNA是否在此过程中发挥作用。大鼠用吗啡训练4天以建立CPP范式。然后连续8天每天进行一次15分钟的测试以进行消退试验。在第8次消退试验后的24小时，大鼠每天接受一次2或100Hz的外周电刺激（PES），持续3天，然后给予1、2或4mg/kg剂量的吗啡激发注射以恢复消退的CPP。在实验结束时，采用半定量RT-PCR技术测定伏隔核（NAc）中PPE和PPD mRNA水平。结果表明，每天30分钟、持续3天给予2Hz和100Hz的PES可抑制吗啡诱导的CPP的表达以及消退后CPP的恢复。2Hz的PES增加了前脑啡肽原（PPE）mRNA水平，而100Hz的PES增加了伏隔核中前强啡肽原（PPD）mRNA水平。这些发现表明，伏隔核中的脑啡肽和强啡肽可能在PES对大鼠吗啡诱导的CPP的表达和恢复的抑制作用机制中发挥重要作用。
