γ-氨基丁酸对情绪应激大鼠额叶皮质一氧化氮合酶和一氧化氮水平的影响

Modulation of emotional stress-induced NOS and NO changes in rat frontal cortex by γ-aminobutyric acid

目的观察γ-氨基丁酸(GABA)对情绪应激大鼠一氧化氮合酶(NOS)和一氧化氮(NO)含量的影响,结合行为学实验,探讨γ-氨基丁酸抗焦虑作用机制。方法将40只雄性Sprague-Dawley(SD)大鼠按随机数字表法分为5组:对照组,模型组,GABA 0.5、1、2 mg/kg组,采用不确定性空瓶刺激的方法建立焦虑大鼠模型,并在应激前分别给予大鼠灌服生理盐水或相应剂量的GABA,14 d后进行旷场实验并分析各组大鼠额叶皮质一氧化氮合酶和一氧化氮水平的差异。结果应激14 d后对照组与其余各组的食物利用率差异极显著(P<0.01);各组大鼠在中央区域的停留时间差异极为显著(P<0.01);对照组、GABA 1 mg/kg和2 mg/kg组进入中央区域的次数显著高于模型组(P<0.05);模型组的修饰次数显著高于GABA 1 mg/kg和2 mg/kg组(P<0.05);总运动距离和直立次数均无显著性差异(P>0.05);对大鼠额叶皮质NOS及NO的分析显示对照组和GABA 2 mg/kg组的NOS活力及NO含量显著高于模型组(P<0.05)。结论 GABA与焦虑大鼠额叶皮质的NOS及NO均呈剂量-效应关系,提示GABA可能通过调节焦虑大鼠额叶皮质中的一氧化氮含量发挥抗焦虑作用。

Objective To observe the effect of γ-aminobutyric acid （GABA） on nitric oxide synthase （NOS） activity and NO level in frontal cortex of rats exposed to emotional stress, and to explore its anti-anxiety mechanisms combining with behavioral test. Methods The rat model of emotional stress was induced by randomly giving empty water bottles. Forty male Sprague-Dawley rats were divided into 5 groups randomly including （n=8） a control group, a model group, and GABA 0.5 mg/kg, 1 mg/kg and 2 mg/kg groups. Rats were pretreated with saline or different doses of GABA orally before suffered from emotional stress. After the treatment for 14 d, animal behaviors were assessed in the open field test, and NOS activity and NO level in frontal cortex of each group were determined. Results After the 14-day-emotional stress treatment, the food utilization rate of the control group was significantly higher than that of the other groups （P〈0.01）, and the time spent at the center of the open field was significantly different among the groups （P〈0.01）. Compared with model group, significantly increased frequency in exploration towards to the center was observed in the control group, GABA 1 mg/kg and 2 mg/kg groups （P〈0.05）. The grooming frequency of the model group was significantly higher than that of the GABA 1 mg/kg and 2 mg/kg groups （P〈0.05）, but the rearing frequency and the total distance traveled in the open field had no significant differences among the groups （P〉0.05）. The NOS activity and NO level were significantly higher in frontal cortex of the control group and GABA 2 mg/kg group as compared with the model group （P〈0.05）. Conclusion GABA has a dose-dependent effect on NOS activity and NO levels in frontal cortex of rats exposed to emotional stress, suggesting GABA may play an anti-anxiety role through modulating NO level in the frontal cortex.