单双侧脑深部电刺激伏核对大鼠海洛因觅药行为的影响

Effects of unilateral and bilateral deep brain stimulation of nucleus accumbens on heroin-seeking behavior in serf-administration rats

目的观察单侧和双侧脑深部电刺激（DBS）伏核核心部对条件性线索和小剂量海洛因诱导大鼠海洛因觅药行为的影响，探讨DBS治疗药物成瘾的单双侧靶点选取问题。方法采用固定比率程序（FR1）建立大鼠海洛因静脉自身给药模型。模型稳定后，将大鼠按照随机数字表法分成对照组、假手术组、左侧DBS组、右侧DBS组和双侧DBS组（每组6只）。各DBS组大鼠行单侧或双侧伏核核心部微电极植入术，术后休息5d，在环境消退期对各DBS组大鼠每天电刺激1h（参数：方波，频率130Hz，电流强度150t．zA，波宽100μs），持续7d。通过比较各组大鼠的有效鼻触数来反映各组大鼠海洛因觅药行为的差异。结果在条件性线索和小剂量海洛因诱导的复吸测评中，各组大鼠有效鼻触反应数之间的差异具有统计学意义（P〈0．05）；右侧DBS组和双侧DBS组大鼠有效鼻触反应数分别与对照组、假手术组和左侧DBS组相比差异具有统计学意义（P〈0．05）；且右侧DBS组大鼠与双侧DBS组有效鼻触反应数之间的差异无统计学意义（P〉0．05）。结论高频电刺激右侧或双侧伏核核心部均能明显抑制条件性线索和小剂量海洛因诱导的大鼠觅药行为；且右侧DBS可获得与双侧DBS相近的疗效。

Objective To investigate the effects of unilateral or bilateral deep brain stimulation （DBS） of nucleus accumbens （NAc） on heroin-seeking behaviors in self-administration rats elicited by conditioned cues or small dose of heroin. Methods Self-administration rat models of relapsing in heroin were established with fixed ration program （FR1）, and then, the rats were randomly divided into 5 groups： control group, sham stimulation group, left DBS group, right DBS group and bilateral DBS group. The concentric bipolar microelectrodes were implanted unilaterally/bilaterally into the core of NAc in rats of DBS groups. After 5 days recovery, the rats were given a 1-hour-long high frequency electrical stimulation （square pulse and frequency： 130 Hz; current intensity： 150 p^A; pulse width： 100 Ixs） for 7 days during the extinction phase. Heroin-seeking behaviors were elicited by conditioned cues or small dose of heroin, and their differences between groups were compared through the times of active nose-poke responses. Results In the reinstatement induced by conditioned cues and small dose of heroin, significant differences on the active nose-poke responses of rats were noted between each two groups （P〈0.05）; both the right DBS group and bilateral DBS group showed significant differences of active nose-poke responses as compared with the control group, the sham stimulation group and the leg DBS group （P〈0.05）, while no significant difference was obsvred between the fight DBS group and the bilateral DBS group （P＇~.05）. Conclusion The right or bilateral DBS of NAt core can significantly reduce the heroin-seeking behaviors elicited by conditioned cues and small dose of heroin in self-administration rats, and the right DBS of NAt can obtain almost the same effects of bilateral DBS.