摘要目的 探讨外源性γ-氨基丁酸(GABA)和舍曲林对急性应激抑郁大鼠海马神经元GABAA(α)受体和GABAB受体的影响.方法 通过迷津试验筛选出认知功能无差异的雄性SD大鼠,随机分成对照组、模型组、GABA组、舍曲林组、GABA+舍曲林组5组.除对照组不做处理外,其他各组于造模前腹腔内分别注射双蒸水、GABA、舍曲林、GABA+舍曲林,并采用强迫游泳建立急性应激抑郁模型,测查各组大鼠的空间记忆保持功能;采用免疫组化法,观察各组大鼠海马CA1、CA3区及DG门区GABA免疫阳性细胞受体数的变化.结果 GABA+舍曲林预作用后,大鼠游泳中不动时间及迷宫中潜伏期较模型组明显缩短,差异有显著性(P<0.01);模型组海马CA1、CA3区,DG 门区的GABAA(α)和GABAB免疫阳性细胞受体数与对照组比较明显减少,差异有显著性(P<0.01);GABA仅增加大鼠海马CA3区GABAB阳性细胞受体数(P<0.01);舍曲林组免疫阳性细胞受体数明显多于模型组(P<0.01);GABA+舍曲林组GABAA(α)和GABAB免疫阳性细胞受体数分别为CAI区[(82.83±8.72)个、(78.08±5.67)个],CA3区[(92.83 ±9.35)个、(76.00±3.97)个],DG门区[(35.00±1.41)个、(33.33±4.36)个]高于其他各组,差异有显著性(P<0.05或0.01).结论 外源性的GABA预作用于急性应激抑郁大鼠,有增强舍曲林抗抑郁、改善认知的作用,其机制可能是通过增强海马GABAA(α)和GABAB阳性细胞受体数发挥作用.

abstractsObjective To study the effects of γ-aminobutyric acid ( GABA) and sertraline on the CABAA(α) receptor and GABAB receptor of hippocampus neuron in rats of depression induced by acute stress. Methods The cognitive function of male SD (Sprague-Dawley) rats was screened through Y-maze. Then rats were randomly divided into five groups. Except control group,rats were injected intraperitoneally with double-distilled, GABA,sertraline or GABA + sertraline respectively. They were exposed to the forced-swimming stress test,which was to make acute stress model of depression. The space memory function in the maze was measured. Then the number of GABA-like immunoreactive neurons in hippocampus CA1 ,CA3 ,DG areas of rats were investigated with immunohistochemist. Results Compared with the model group,the immobility time in the forced-swimming test and the latency in the maze could be reduced significantly after pretreatment with GABA and sertraline (P < 0.01). The positive cell populations of CA1 ,CA3 region and DG gate region in the model group were significantly reduced compared with the control group (P<0.01). GABA could only improve the positive cell populations of GABAB receptor in CA3 region (P<0.01). In the sertraline group,the positive cell populations in hippocampus were increased obviously more than it in model group(P<0.01). The positive cell populations of hippocampus in the GABA + sertraline group in CA1 ( (82.83±8.72),(78.08±5.67)),in CA3((92.83±9.35),(76.00±3.97)),in the gate of DG( (35.00 ±1.41) ,(33.33±4.36)) increased significantly to the other groups (P< 0.05 or 0.01). Conclusion Ectogenic GABA could improve the sertraline' s effects of antagonizing acute depression effectively and the space memory function,and its mechanism may be involved in strengthening the expression of GABAA(α) receptor and GABAB receptor in hippocampus.