微清蛋白中间神经元在氯胺酮抗抑郁中的作用

目的:观察微清蛋白(PV)中间神经元在氯胺酮抗抑郁中的作用。方法:32只Wistar雄性大鼠随机均分为4组(n=8),包括生理盐水组(S组)、氯胺酮组(K组)、夹竹桃麻素预处理+生理盐水组(AS组)、夹竹桃麻素预处理+氯胺酮组(AK组)。夹竹桃麻素预处理组将药物溶于大鼠饮水中,共喂养1周,于第8 d制备模型。大鼠强迫游泳15 min制备急性应激抑郁模型,24 h后给大鼠分别腹腔注射1 mL生理盐水或氯胺酮10 mg/kg,给药后0.5 h行敞箱实验记录大鼠水平运动及垂直运动得分,行强迫游泳6 min记录后5 min内不动时间。行为学测试结束后,取大鼠前额皮层,Western印迹检测PV中间神经元中PV及谷氨酸脱羧酶67(GAD67)的表达。结果:与S组相比,K组大鼠强迫游泳不动时间减少,PV及GAD67的表达下降(P0.05),AS组则无显著变化(P0.05);与K组相比,AK组大鼠强迫游泳不动时间增加,PV及GAD67的表达增加(P0.05)。生理盐水、氯胺酮、夹竹桃麻素均未显著影响大鼠自主活动(P0.05)。结论:氯胺酮通过下调大鼠前额皮层PV中间神经元功能发挥快速有效的抗抑郁作用。

Role of Parvalbumin Interneurons in the Antidepressant Effects of Ketamine

Objective： To investigate the roles of parvalbumin（PV） interneurons in the antidepressant effects of ketamine. Methods： Thirty two male Wistar rats were equally randomized into 4 groups（n=8 each）： saline group （S group）, ketamine group（K group）, apoeynin pretreatment ＋ saline group（AS group）, and apocynin pretreatment ＋ ketamine group（AK group）. The forced swimming test（FST） of 15 min was used to establish a rat depression model. Apocynin was given in the drinking water for a total of seven days in the apocynin pretreatment groups and the model was established in the eighth day. Twenty four hours after the FST, saline or ketamine （10.0 mg/ kg） of 1 mL was intraperitoneally injected, respectively. The open field test was carried out and the crossing and the rearing scores were recorded, and the FST of 6 min was carried out in which the immobility time in last 5 min of the rats was recorded at 0.5 h after drug intervention. The animals were then decapitated and the prefron- tal cortex was harvested, and the double immunofluoreseenee method was used for determination of PV and glutamie acid decarboxylase 67（GAD67） expressions in the PV interneurons. Results： Compared with the S group, the immobility time and the expressions of PV and GAD67 decreased in the K group（P〈0.05）, whereas there was no significant difference in the AS group（P〉0.05）. Compared with the K group, the immobility time and the expressions of PV and GAD67 increased in the AK group（P〈0.05）. Saline, ketamine, or apoeynin did not affect the locomotor activity of rats（P〉0.05）. Conclusion： Ketamine exerts robust and rapid antidepressant effects through the down-regulation of PV interneurons in the prefrontal cortex in rats.