不同时长应激对大鼠抑郁样行为及内侧前额叶皮层CB1及GluA1表达的影响

Effects of stress of different duration on depression-like behavior and expression of CB1 and GluA1 in medial prefrontal cortex of rats

目的:探究不同时间内慢性不可预见性温和应激(CUMS)诱导的抑郁模型大鼠内侧前额叶皮层(mPFC)中大麻素受体CB1与AMPA受体亚基GluA1的变化。方法:将30只大鼠随机分为3组,3周模型组给予3周CUMS法造模,4周模型组给予4周CUMS造模,对照组不做任何处理。进行糖水偏爱、新颖抑制摄食和强迫游泳实验来检测各组大鼠行为学的变化,通过Western blot技术检测mPFC脑区突触体中CB1和GluA1蛋白表达。结果:与对照组相比,大鼠经历4周CUMS后糖水偏爱率降低、新颖抑制摄食测试中摄食潜伏期延长,强迫游泳测试中不动时间增加,而经历3周CUMS后大鼠行为学较对照组无明显差异,提示4周CUMS后抑郁大鼠造模成功。4周CUMS应激后可降低4周模型组mPFC脑区突触体中CB1及GluA1蛋白表达水平(P<0.05),而3周模型组CB1及GluA1表达水平和对照组无明显差异。结论:4周应激后制备抑郁动物模型大鼠最为稳定,慢性应激导致的抑郁与mPFC脑区中CB1和GluA1表达密切相关。

Objective:To explore the changes of cannabinoid receptor(CB1)and AMPA receptor subunit GluA1 in the medial prefrontal cortex(mPFC)of depression model rats induced by chronic unpredictable mild stress(CUMS).Methods:A total of 30 rats were randomly divided into three groups. The three-week model group was given a three-week CUMS model,the four-week model group was given a four-week CUMS model,and the control group was given no treatment. The behaviors of rats were detected in each group,and the expression of CB1 and GluA1 protein in synaptosomes in mPFC brain region was detected by Western blot.Results:Compared with the control group,the surcose preference decreased,the feeding latency increased in the novel inhibition feeding test,and the immobility time increased in the forced swimming test in the four-week model group. However,after three weeks of CUMS,there was no obvious change in the behavior of rats compared with the control group,suggesting that four-week model of CUMS was successful. CUMS can reduce the expression level of CB1 and GluA1 protein in synaptosomes of mPFC brain area in four-week model group(P<0.05),but there was no significant difference between three-week model group and control group.Conclusion:Four-week CUMS was more likely to lead to depressive-like behavior in rats,which may be closely related to the expression of CB1 and GluA1 in mPFC.