咖啡因对大鼠神经行为学及海马神经元内γ-氨基丁酸和5-羟色胺表达的影响

Effect of caffeine on neuroethology and the expression of gamma-aminobutyric acid and 5-hydroxytryptamine in hippocampal neurons of rats

目的 观察不同剂量咖啡因对大鼠神经行为学及海马神经元内^γ-氨基丁酸（GABA）和5-羟色胺表达的影响.方法 将30只雌性SD大鼠按完全随机分组法分成3组,对照组（n=10）每天给予生理盐水灌胃,实验组分低剂量组（n=10）和高剂量组（n=10）,每天分别给予20、60 mg/kg咖啡因灌胃,连续18 d,进行咖啡因干预处理.通过Morris水迷宫实验测试各组大鼠的学习记忆能力,运用免疫组织化学方法观察各组大鼠海马神经元内GABA和5-羟色胺表达变化.结果 Morris水迷宫实验结果显示,咖啡因可以改善大鼠学习记忆能力,高剂量咖啡因作用更加显著,差异具有统计学意义；免疫组织化学染色显示,高剂量组（0.214 1±0.006 6）和低剂量组（0.279 4±0.008 1）海马神经元内GABA表达较对照组（0.355 1 ±0.011 7）减少（F=172.603,P＜0.05）；高剂量组（0.551 3 ±0.017 8）和低剂量组（0.485 6 ±0.008 5）5-羟色胺表达较对照组（0.290 3 ±0.009 7）增多（F=289.541,P＜0.05）,且高剂量组变化更加明显.结论 咖啡因可剂量依赖性地改善大鼠学习记忆能力,其作用机制可能与抑制海马神经元内GABA表达和促进5-羟色胺表达有关.

Objective To observe the effects of caffeine on neuroethology and the expression of gamma-aminobutyric acid （GABA） and 5-hydroxytryptamine （5-HT） in the hippocampal neurons of rats.Methods Thirty female Sprague-Dawley rats were randomly devided into three groups including control group,low-dose group and high-dose group.The rats in control group were given a gavage of normal saline daily while the rats in low-dose group and high-dose group were given a gavage daily of 20 mg/kg and 60 mg/kg caffeine respectively for 18 days.All the rats were submitted to behavioral testing for learning and memory ability in the Morris water maze.The expression of GABA and 5-HT in the hippocampal neurons were observed by immunohistochemical staining.Results Caffeine could improve the learning and memory ability of rats in the Morris water maze,and high-dose caffeine was more efficient.The expression of GABA in highdose group （0.214 1 ±0.006 6） and low-dose group（0.279 4 ±0.008 1） decreased compared with control group（0.355 1 ±0.011 7,F=172.603,P 〈 0.05）;While that of 5-HT in high-dose group （0.551 3 ± 0.017 8） and low-dose group （0.485 6 ± 0.008 5） increased compared with control group （0.290 3 ± 0.009 7,F =289.541,P 〈 0.05）.Conclusions Caffeine can dose-dependently improve the learning and memory ability of rats,which might be involved with suppressing the expression of GABA and promoting that of 5-HT in the hippocampal neurons of rats.