高频电刺激下丘脑后核对氟哌啶醇致大鼠运动不能的影响

目的：利用氟哌啶醇致僵直大鼠模拟帕金森病（PD）的运动不能，通过高频电刺激下丘脑后核（PH），观察大鼠僵直和运动能力的变化，从而探讨PH在PD治疗中潜在的应用价值。方法：将成年雄性SD大鼠随机分为PH刺激组、假刺激组和对照组，对PH刺激组和假刺激组大鼠双侧PH置入双极刺激电极，腹腔注射氟哌啶醇30min后，PH刺激组给予持续高频电刺激（130Hz，60μs，100μA），分别利用爬杆实验和跑步机实验评价大鼠僵直程度和运动能力。结果：腹腔注射氟哌啶醇1．0mg／kg后，①大鼠呈僵直状态，其潜伏期为167．88±17．88S，给予双侧PH高频电刺激后潜伏期显著缩短至77．5±21．27s（P〈0．01）。②跑步机试验显示大鼠跑动速度和跑动距离显著下降，分别为5．78±0．90cm／s和8．06±4．35m（P〈0．01），给予双侧PH高频电刺激后显著提高跑动速度和跑动距离，分别为12．72±3．66cm／s和98．61±96．75m（P〈0．01）。结论：腹腔注射氟哌啶醇可模拟帕金森病的僵直和运动不能症状，双侧高频电刺激PH可显著拮抗氟哌啶醇对大鼠僵直和运动不能的作用，提示PH为DBS治疗帕金森病运动不能的有效刺激靶点，为临床DBS刺激PH治疗PD提供实验依据。

The Effect of High Frequency Stimulation of Posterior Hypothalamic Nucleus in Haloperidol-induced Akinesia rats

Objective： To explore the potential target for deep brain stimulation （DBS） in the treatment of Parkinson＇s disease by observing changes after bilateral high frequency stimulation of the posterior hypothalamic nucleus （PH） post injection of haloperidol. Methods： Adult male SD rats were randomly divided into three groups： haloperidol and PH stimulation group （HAL±Stim）, haloperidol group （HAL） and saline group （Saline）. Bipolar stimulation electrodes were bilaterally implanted into PH in PH stimulation group. Rats in all three groups were injected with haloperidol and then the degree of catalepsy and akinesia were evaluated by bar test and treadmill test, respectively. In the stimulation group, PH was bilaterally given high frequency stimulation （130 Hz, 60 μS, 100 μA） during behavioral tests. Results： Thirty minutes after injection ofhaloperidol （1.0 mg/kg）, rats were catalepsy. The treadmill tests showed that the velocity and distance were significantly reduction in haloperidol treatment rats. And bilateral PH high frequency stimulation significantly reduced the degree of catalepsy as well as improved the velocity and distance in treadmill test. Thirty minutes after injection ofhaloperidol （1.0 mg/kg）, （1） Rats were catalepsy with the latency of 167.88± 17.88 s. Bilateral PH high frequency stimulation （130 Hz, 60 μs,100 μA） significantly reduced the latency to 77.5± 21.27 s （P〈0.01）. （2）The treadmill tests showed that the velocity and distance were significantly reduced, at 5.78± 0.90 cm/s and 8.06± 4.35 m respectively （P〈0.01）. And bilateral PH high frequency stimulation significantly improved the velocity and distance in treadmill test to 12.72± 3.66 cm/s and 98.61 ± 96.75 m, respectively （P〈0.01）. Conclusion： Injection of haloperidol mimics the catalepsy and akinesia symptoms of Parkinson＇s disease. High frequency stimulation of PH can significantly reduce haloperidol-induced catalepsy and improve locomotion, suggesting that PH is a potential stimulation target for DBS in the treatment of PD which provides the experimental basis for treatment PD by PH-DBS ultimately.