目的:观察氯胺酮对强迫游泳大鼠前额皮层谷氨酸及γ-氨基丁酸的影响.方法:32只Wistar雄性大鼠随机均分为4组(n=8):生理盐水0.5 h组(S05组)、生理盐水2h组(S2组)、氯胺酮0.5 h组(K0.5组)、氯胺酮2h组(K2组).药物干预前1d大鼠行强迫游泳15 min制备急性应激抑郁模型.药物干预当天,给大鼠分别腹腔注射1 mL容积的生理盐水或氯胺酮10 mg/kg,给药后0.5 h及2h分别再次行强迫游泳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,检测谷氨酸及γ-氨基丁酸的含量.结果:与S05组相比,K05组大鼠强迫游泳不动时间显著减少,谷氨酸含量上升,γ-氨基丁酸含量下降(P＜0.05).与S2组相比,K2组大鼠强迫游泳不动时间显著降低(P＜0.05),谷氨酸及γ-氨基丁酸含量则无明显变化(P＞0.05).结论:氯胺酮在大鼠强迫游泳模型中能够发挥快速抗抑郁作用,同时伴随大鼠前额皮层谷氨酸上调及γ-氨基丁酸下调.%Objective To observe the effects of ketamine on glutamate and GABA in prefrontal cortex of rats receiving forced swimming test (FST). Methods 32 male Wistar rats were randomized into 4 groups (each n = 8); saline 0.5 h group (S05 group), saline 2 h group (S2 group), ketamine 0.5 h group (K0.5 group), ketamine 2 h group (K2 group). The FST lasted for 15 min was used to establish rat depression model. On the next day, saline or ketamine (10.0 mg/kg) of lmL were intraperitoneally injected, then 0.5 h and 2 h later, the FST of 6 min was carried out and the immobility time within 5 min during the FST was recorded. The animals were then decapitated and the prefrontal cortex was harvested for determination of glutamate and γ-aminobutyric acid levels. Results Compared with those in S0.5 group, the immobility time was decreased, the content of glutamate was increased and the content of γ-aminobutyric acid was decreased significantly in K0.5 group (P < 0.05). Compared with those in S2 group, the immobility time was decreased significantly (P < 0.05) , the content of glutamate and γ-aminobutyric acid had no significant changes in K2 group (P > 0.05). Conclusion Ketamine possessed significant and rapid antidepressant effects in rats receiving FST, which was associated with the increase of glutamate and the decrease of γ-aminobutyric acid levels in prefrontal cortex.
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