脑深部电刺激双侧伏核对吗啡成瘾大鼠复吸行为的影响
Effects of deep brain stimulation of bilateral nucleus accumbens on the behavior of relapse in morphine-dependent rats
摘要目的 研究脑深部电刺激双侧伏核核心部对吗啡成瘾大鼠复吸行为的影响.方法 手术前筛选大鼠,筛选后大鼠随机分为空白组、空白电刺激组、吗啡组、吗啡假手术组、吗啡电刺激组.电极植入7d后采用隔日递增原则皮下注射吗啡(5mg/kg起始,每次递增5mg/kg,至20mg/kg稳定)建立大鼠吗啡成瘾模型.通过改进后的DBS电路进行电刺激,刺激参数为130Hz、150A、60s、1 h/d、14d.干预前后变化由条件位置偏爱实验检测.复吸行为采用小剂量吗啡(3 mg/kg)诱导,24h后再次检测CPP.数据统计采用two-way ANOVA,组间比较用Bonferroni方法.结果 ①完成CPP训练后,吗啡组、吗啡假手术组、吗啡电刺激组三个组的CPP评分为(155.87±20.45)s、(107.33 ± 18.10)s、(135.45±22.09)s,与前两组均有明显差异[与空白组(-70.34±15.40)s比较t值和P值分别为:t=9.45,P<0.01;t=6.94,P<0.01;t=8.04,P<0.01].②7天DBS后,吗啡电刺激组大鼠CPP评分与吗啡组(t=4.21,P<0.01)、吗啡假手术组(t=1.10,P<0.05)差异明显.14d DBS后差异更加明显(t=5.15,P<0.01;t=3.92,P<0.01).③给予小剂量吗啡诱导复吸后,吗啡电刺激组CPP评分小于吗啡组(t=4.04,P<0.01)和吗啡假手术组(t=4.13,P<0.01)组,且与空白组(-53.50 ± 11.10)s(t=2.60,P>0.05)差异无显著性,但与空白电刺激组(t=3.70,P<0.01)仍差异有显著性.结论 DBS双侧伏核核心部不仅可以干预吗啡成瘾大鼠的CPP行为,而且能抑制小剂量吗啡诱导的复吸行为.
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abstractsObjective To investigate the influence on the behavior of withdrawal and relapse after deep brain stimulation of bilateral nucleus accumbens in morphine-dependent rats. Methods The rats with a strong unconditioned preference were discarded in preconditioning test, the selected rats were distributed into five groups randomly. After operation,morphine hydrochloride was injected subcutaneously into SD rats for 12 days (once every day,initial 5 mg/kg,increasing by 5 mg/kg per time,stable in 20 mg/kg ). A modified electrical circuit was used to procedure the DBS,the parameter was 130 Hz,150 A,60 s,l h/d,14 d. CPP test was used to exam the effect of DBS. A minor morphine dose (3 mg/kg) was injected to induce the behavior of relapse, and CPP was tested again after 24 h. Two-way ANOVA was performed on the data with Bonferroni posttest. Result ①After CPP training,CPP score of group morphine, morphine + sham and morphine + DBS was ( 155. 87 ± 20. 45 ) s, (107.33 ± 18.10)s,(135.45 ±22.09)s,and had significant difference with group of control( ( -70.34 ± 15.40) s)(t = 9.45,P<0.01; t = 6.94,P<0.01;t = 8.04,P<0.01).②After 7 days' DBS,the CPP score in group of morphine + DBS reduced significantly compared to group of morphine( t = 4.21, P<0.01) and morphine + sham( t=1.10, P<0.05).0n the 14th day,there was more pronounced reduction ( t = 5. 15, P<0.01; t = 3.92, P< 0.01). ③ 24 hours after the minor morphine dose was injected,the CPP score in morphine + DBS didn't increase significantly, and had significant difference with group of morphine ( t = 4.04, P<0.01) and morphine + sham ( t= 4. 13, P<0.01). Conclusion DBS bilateral nucleus accumbens in morphine-dependent rats can interfere the behavior of morphine-induced CPP and relapse.
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