褪黑素对抑郁大鼠行为学及单胺类神经递质影响

Influence of Melatonin on Praxeology and Monoamine Neurotransmitters of Depressed Rats

目的:探究褪黑素(MT)对慢性不可预见温和应激模型(CUMS)抑郁大鼠的行为学及海马内单胺类神经递质影响。方法:选取60只健康雄性SD大鼠随机分为空白组(0.9%氯化钠溶液)、模型组(0.9%氯化钠溶液)、氟西汀阳性对照组(氟西汀2.1 mg/kg)、MT低剂量组(MT 10 mg/kg)、MT中剂量组(MT 20 mg/kg)、MT高剂量组(MT 40 mg/kg),每组10只,腹腔注射给药,连续6周。除空白组外,其余各组均在给药同时配合CMUS法复制抑郁模型。在第0、14、28、42 d通过大鼠体重变化、糖水偏好实验(SPT)、旷场实验(OFT)和强迫游泳实验(FST)测试大鼠的抑郁行为改变,并通过ELISA法检测各组大鼠海马多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)的含量测定其脑内单胺类神经递质含量。结果:模型组第14、28、42天的体重均低于空白组(P<0.05)。与空白组相比,第28、42天模型组的糖水偏好率、后4 min内运动总路径、中央运动路径、后4 min挣扎时间比均降低(P<0.05)。与模型组相比,氟西汀阳性对照组、MT低、中、高剂量组第28、42天体重、糖水偏好率、后4 min内运动总路径、中央区运动域路径、后4 min挣扎时间比均升高(P<0.05)。第42天MT高剂量组体重、糖水偏好率、后4 min内运动总路径、中央区运动域路径、后4 min挣扎时间比均高于MT中、低剂量组(P<0.05)。与空白组相比,模型组海马DA、NE、5-HT含量均下降(P<0.05);与模型组相比,氟西汀阳性对照组、MT低、中、高剂量组的DA、NE、5-HT含量均升高(P<0.05)。MT高剂量组的DA、NE、5-HT含量均高于MT中、低剂量组(P<0.05)。结论:MT具有改善抑郁大鼠行为学的作用,作用机制可能与其影响脑内单胺类神经递质的含量有关,且MT改善抑郁作用可能存在的剂量效应关系。

Objective:To explore the influence of melatonin(MT)on the behavior and monoamine neurotransmitters in depressed rats under hippocampus of chronic unpredictable mild stress model(CUMS).Method:Sixty healthy male SD rats were randomly divided into blank group(0.9%sodium chloride solution),model group(0.9%Sodium Chloride Solution),Fluoxetine positive control group(2.1 mg/kg),MT low dose group(MT 10 mg/kg),MT medium dose group(MT 20 mg/kg)and MT high dose group(MT 40 mg/kg),10 in each group,intraperitoneal injection for 6 weeks.Except blank group,depression model was replicated in other groups with CMUS method at the same time.At 0,14,28 and 42 days,the changes of body weight,sugar water preference test(SPT),open field test(OFT)and forced swimming test(FST)were used to test the changes of depressive behavior in rats.The contents of dopamine(DA),norepinephrine(NE)and 5-hydroxytryptamine(5-HT)in hippocampus were determined by ELISA.Result:The body weight on day 14,28 and 42 of model group were lower than those of blank group(P<0.05).Compared with blank group,sugar water preference rate,total exercise path in the last 4 min,central exercise path and struggle time ratio in the last 4 min in model group were all decreased on day 28 and 42(P<0.05).Compared with model group,the body weight,sugar water preference rate,total movement path in the last 4 min,central movement area path and struggle time in the last 4 min in Fluoxetine positive control group,low,medium and high dose MT groups were increased on day 28 and 42(P<0.05).On day 42,the body weight,sugar water preference rate,total movement path in the last 4 min,movement area path in the central region and struggle time ratio in the last 4 min in the MT high dose group were higher than those in the MT medium dose and low dose groups(P<0.05).Compared with blank group,the contents of DA,NE and 5-HT in hippocampus of model group were decreased(P<0.05).Compared with model group,the contents of DA,NE and 5-HT in fluoxetine positive control group,MT low,medium and high dose groups were increased(P<0.05).The contents of DA,NE and 5-HT in MT high dose group were higher than those in MT medium dose and low dose groups(P<0.05).Conclusion:MT can improve the behavior of depressed rats,and the mechanism of which may has a close correlation with its effect on the content of monoamine neurotransmitters in the brain.There may be a dose effect relationship between MT and depression.