异丙酚条件性位置偏爱效应形成的神经机制

Effect of propofol on affective state as assessed by conditioned place preference

目的 异丙酚是否可引起精神依赖性尚不清楚,本研究利用条件性位置偏爱实验模型评价异丙酚的精神依赖性。方法 48只小鼠分成4组,分别给予不同剂量的异丙酚（0,50mg/kg、75mg/kg和100mg/kg）,在腹腔注射后,观察条件性位置偏爱箱停留的时间,判断小鼠精神依赖的情况。应用免疫组化的方法检测小鼠中枢不同脑区即刻早基因（c-fos）的表达水平。结果 50mg/kg和100mg/kg异丙酚组伴药盒有位置偏爱的趋势,仅75mg/kg组于伴药盒位置偏爱停留箱停留时间（214±72）s与正常组（121±49）s有明显差异（P<0.01）。应用免疫组化技术观察75mg/kg组小鼠中枢额前叶皮质和梨状皮质c-fos基因表达呈阳性。结论 异丙酚具有一定的成瘾性,但与以往经典的伏隔核-腹侧被盖多巴胺奖赏系统无关,可能存在其它新的传导通路。

ve It was suggested that propofol induces a subjective feeling of well-being at subanesthetic doses and during recovery from anesthesia. Whether propofol produces a pleasant affective state remains to be determined. In the current study the effect of subanesthetic and anesthetic does of propofol on affective state in mice was assessed by conditioned place preference. Methods The place conditioning apparatus consisting of two compartments (white and black) with a removable partition between them was made according to Reid. Animals were placed in the apparatus and allowed to move freely between the white and black compartments for 15 min. The animals which preferred to spend more time in the black compartment were chosen. Forty-eight male kunming mice weighing 20-25mg were divided into 4 groups(n=12): control group and 3 propofol groups (50,75, 100mg·kg-1).The place conditioning lasted 8 days before test. During conditioning phase the partition between the two compartments was in place. In propofol groups animals received propofol on one day and were placed in the white compartment for 50 min and on the alternate day the animals received emulsion (the vehicle of propofol) and were placed in the black compartment. In control group the animals received only emulsion and were placed in white and black compartment alternately. During test the partition between the two compartments was removed. Animals were placed in the white compartment for 10 min then propofol or emulsion was given intraperitoneally(IP). 5 min later the animals were placed back in the apparatus and stayed for 15 min. The time spent by the animal in the white compartment was recorded. The expression of c-fos gene in different brain areas was measured by immuno-histochemical technique. Results In propofol groups there was a tendency of place preference but only in propofol 75mg·kg-1 group the time spent by mice in the white compartment( 214±72) s was significantly longer than that in control group (121±49)s (P<0.01). Propofol induced c-fos gene expression in frontal and piriform cortex.Conclusions Propofol 75 mg·kg-1 induces a pleasant affective state in mice which could be indicative of potential abuse. The mechanism is different from that addiction.