谷氨酸及γ-氨基丁酸在氯胺酮致大鼠精神分裂样表现中的变化

Changes of Glutamate and GABA in Ketamine-induced Psychosis-like Responses in Rats

目的:观察大鼠前额皮层谷氨酸(Glu)及γ-氨基丁酸(GABA)在氯胺酮致精神分裂样表现中的变化。方法:雄性Wistar大鼠32只随机分为生理盐水组(S组,n=16)和氯胺酮组(K组,n=16)。腹腔注射生理盐水或氯胺酮30 mg/kg(容积1 mL),一天一次,连续5天,最后一次给药后0.5 h及2 h分别通过敞箱实验观察大鼠自主活动,并记录刻板行为评分。行为学测试后,取大鼠前额皮层,检测Glu及GABA含量。结果:与S组比较,K组大鼠给药后0.5 h自主活动增强、刻板行为评分增高(P<0.05),符合精神分裂症大鼠表现;给药后2 h行为学评分则无显著差异(P>0.05);给药后0.5 h及2 h大鼠前额皮层Glu水平均增加、GABA水平均下降(P<0.05)。与氯胺酮给药后0.5 h组相比,给药后2 h Glu水平下降(P<0.05)、GABA水平则无显著差异(P>0.05)。结论:氯胺酮致精神分裂样表现可能与大鼠前额皮层Glu增加及GABA减少有关。

Objective： To observe the changes of prefrontal glutamate and gamma-aminobutyric acid （GABA） levels in ketamine- induced psychosis-like responses in rats. Methods： Thirty two male Wistar rats were randomized into saline group （S group, n=16） and ketamine group （K group, n=16）. Saline 1 ml and ketamine 30 mg/kg （1 ml） were intraperitoneally given every day for 5 days. Autonomic activities were observed during open field test at 0.5 h and 2 h after the last administration, the scores of stereotyped behavior were also recorded. The prefrontal cortex was harvested after behavioral test for the determination of glutamate and GABA levels. Result： Compared with the S group, rats in the K group showed significant increase of autonomic activities at 0.5 h after the last administration, scores of stereotyped behavior showed significant increase （P〈0.05）, which were consistent with the psychosis performance in rats. Behavioral scores had no significant difference at 2 h after the last administration between the two groups （P〉0.05）. The prefrontal glutamate level increased and GABA level decreased at 0.5 h and 2 h after ketamine administration （P〈0.05）. Compared with the K group of 0.5 h after administration, the K group of 2 h had a lower level of glutamate （P〈0.05）, but had no significant difference in respect of GABA level（ P〉0.05）. Conclusion： Increased glutamate level and decreased GABA level in rats prefrontal cortex may contribute to ketamine-induced psychosis-like responses in rats.