摘要
目的通过观察多巴胺D2受体(DRD2)基因敲除小鼠在行为学实验中的认知、焦虑等探索相关行为,以分析其在高级精神活动中的作用。方法选择DRD2基因敲除小鼠为DRD2基因敲除组,并设正常小鼠为对照组。分别通过六臂水迷宫、新物体识别糖水消耗、明暗箱操作实验及血清5-羟色胺(5-HT)、糖皮质激素及额叶皮质及纹状体中的DRD2 mRNA表达检测对比2组小鼠的认知及情绪样行为。结果①DRD2基因敲除组小鼠逃避潜伏期时长[(42.15±5.22)s vs.(23.14±3.51)s]以及入臂错误数[(5.39±1.31)次vs.(1.41±1.20)次]均较对照组显著增加(P<0.05);②基因敲除组第二阶段[(55.84±14.13)s vs.(30.76±10.23)s]、第三阶段探索时间[(69.41±22.34)s vs.(42.36±11.62)s]均显著大于对照组(P<0.05),DR[(38.12±6.44)%vs.(56.85±6.28)%]显著低于对照组(P<0.05);③敲除DRD2基因组糖水消耗率(74.78±7.22)%,明显高于对照组(39.28±3.77)%(P<0.05);④基因敲除组较对照组的明暗箱穿梭次数[(27.93±8.11)次vs.(17.30±6.17)次]明显增多、明箱停留时间[(30.22±0.18)s vs.(20.44±0.12)s]显著延长(P<0.05);⑤基因敲除组的5-HT水平较对照组明显降低[(130.22±7.14)μg/L vs.(165.13±7.21)μg/L],糖皮质激素明显升高[(37.51±4.35)mmol/L vs.(26.34±4.72)mmol/L](P<0.05);⑥基因敲除组小鼠额叶皮质及纹状体中的DRD2 mRNA表达明显低于对照组(0.38±0.09 vs.1.12±0.25,0.45±0.10 vs.1.29±0.31,P<0.05)。结论敲除DRD2基因可使小鼠的额叶皮质及纹状体中的DRD2 mRNA水平降低,空间学习记忆水平降低,学习记忆能力降低,焦虑、抑郁样情绪增多,血清5-HT水平、糖皮质激素水平升高,该基因在小鼠认知及情绪样行为中发挥重要作用。
Objective To investigate the related behaviors of dopamine D2 receptor(DRD2)gene knockout mice in behavioral experiments,in order to explore their role in advanced mental activities.Methods DRD2 knockout mice were selected as the DRD2 gene knockout group,and normal mice were selected as the control group.Six-arm water maze experiment,new object recognition experiment,sugar and water consumption experiment,light-dark box test,5-hydroxytryptamine(5-HT),glucocorticoids and detection of DRD2 mRNA expression in the frontal cortex and striatum were evaluated the cognitive and emotional behavior of DRD2 knockout mice and normal control mice.Results①The duration of the escape latency[(42.15±5.22)s vs.(23.14±3.51)s]and the number of arm errors[(5.39±1.31)times vs.(1.41±1.20)times]in the DRD2 knockout group mice were significantly increased compared with the control group(P<0.05);②The exploration time in the second[(55.84±14.13)s vs.(30.76±10.23)s]and third[(69.41±22.34)s vs.(42.36±11.62)s]of the gene knockout group was significantly longer than that of the control group(P<0.05),and the DR value[(38.12±6.44)%vs.(56.85±6.28)%]was significantly lower than that of the control group(P<0.05);③The sugar and water consumption rate of the knockout DRD2 gene was(74.78±7.22)%,which was significantly higher than that of the control group(39.28±3.77)%(P<0.05).④The number of light and dark box shuttles[(27.93±8.11)times vs.(17.30±6.17)times]in the gene knockout group increased significantly,and the residence time[(30.22±0.18)s vs.(20.44±0.12)s]was significantly extended(P<0.05);⑤The 5-HT expression[(130.22±7.14)μg/L vs.(165.13±7.21)μg/L]in the knockout group was significantly lower than control group,and the glucocorticoids[(37.51±4.35)mmol/L vs.(26.34±4.72)mmol/L]were significantly higher than control groupincreased(P<0.05);⑥The expression of DRD2 mRNA in the prefrontal cortex and striatum of the knockout group was significantly lower than that in the control group(0.38±0.09 vs.1.12±0.25,0.45±0.10 vs.1.29±0.31,P<0.05).Conclusion The deletion of DRD2 gene could reduce the mRNA level of DRD2 in the prefrontal cortex and striatum,decrease the spatial learning and memory level,decrease the learning and memory ability,increase the anxiety and depression-like emotions,increase the serum 5-HT level,and increase the glucocorticoid levels in mice.The DRD2 gene plays an important role in the cognition and emotion-like behavior of mice.
作者
潘永花
王军瑞
王雪
PAN Yong-hua;WANG Jun-rui;WANG Xue(Department of Psychiatry,Third People's Hospital of Qinghai Province,Xining Qinghai 810007,China;Department of Traditional Chinese Medicine,Medical College of Qinghai University,Xining Qinghai 810016,China)
出处
《临床和实验医学杂志》
2020年第24期2593-2597,共5页
Journal of Clinical and Experimental Medicine
基金
青海省科协科技创新智库决策咨询调研课题项目(编号:2019KX07)。
