目的研究高频电刺激双侧伏隔核对吗啡成瘾大鼠复吸行为的影响。方法成年SD大鼠20只,电极外套管通过立体定向手术植入大鼠双侧伏隔核,术后休息5d,应用腹腔注射吗啡(10mg/kg)诱导建立吗啡成瘾大鼠位置偏爱(CPP)模型,建模成功后用生理盐水替代吗啡进行熄灭训练。CPP检测确定消退成功后,将大鼠随机分成实验组(吗啡+DBS)和对照组(吗啡+假刺激),通过DBS电路给予电刺激,实验组给予高频电刺激,对照组予假刺激,连续刺激7d。末次刺激后24h内给予小剂量吗啡诱导复吸。结果(1)大鼠建模后CPP评分[(616.2±74.7)s]较建模前CPP评分[(353.9±84.3)s]升高,差异有统计学意义(P〈0.01)。(2)消退CPP评分与建模后评分降低[(456.4±148.8)s vs(616.2±74.7)s,P=0.0219],与建模前评分[(353.9±84.3)s]相比,差异无统计学意义(P=0.0847)。(3)末次刺激24h内给予小剂量吗啡诱导复吸,实验组复吸评分较对照组复吸评分降低[(330.1+212.6)s vs(684.24.230.2)S,P=0.0029],复吸得到抑制。结论戒断期高频刺激成瘾大鼠双侧伏隔核会抑制大鼠点燃复吸行为。
Objective To investigate the effect of high frequency stimulation of bilateral nucleus accumbens on relapse behaviors in morphine-dependent rats. Methods Twenty adult SD rats were employed in the experiment. Through stereotactic operation, outer electrode cannula was implanted into rats' bilateral nucleus accumbens. After 5 days of rest, the morphine-dependent rat model with conditioned place preference (CCP) was established through intraperitoneal morphine injection ( 10 mg/kg). After acquisition of CPP, normal saline was replaced with morphine for CPP extinction training. CPP test was used to exam the effect of extinction. The rats,after being randomly divided into experimental group (morphine±DBS) and control group (morphine±sham DBS) ,were electrically stimulated using modified DBS circuits. Rats in the experimental group were given high frequency electrical stimulation while the control group was sham stimulation. After consecutive stimulation for 7 days, rats in the two groups were given small dose of morphine (3 mg/kg) to trigger relapse. Results ( 1 ) The CPP score increased after the establishment of rat models compared with pre-establishment of the rat models ( ( 616.2±74.7) s vs ( 353.9 ± 84.3 ) s, P〈 0.01 ). (2) The CPP score after extinction training decreased compared with pre-conditioned CPP score ( (456.4± 148.8) s vs ( 353.9± 84.3) s), P= 0.0847) and had no statistical difference compared with post-conditioned CPP score ( (456.4± 148.8 ) s vs (616.2±74.7) s, P= 0.0219). ( 3 ) When the relapse was induced by small doses of morphine within 24h after the last stimulation,the CPP score of the experimental group decreased compared with the CPP score of control group ( (330.1±212.6) s vs (684.2±230.2) s, P= 0.0029 ), and the relapse was restrained. Conclusion High frequency DBS of bilateral nucleus accumbens can attenuate relapse behavior in rats .