An Animal Model Of Anxiety Depression And The Establishment Of A Multi-level Evaluation System

Objective:According to the clinical and multiple pathogenesis of anxious depression,an animal model of anxiety and depression was established by chronic psychological stress combined with drug stimulation.From animal behavior,blood biochemistry,histomorphology and molecular biology,The evaluation system of the model was established.A new animal model of anxious depression was established by using near primate tree shrew which is close to the human clinical.Methods:1.66 SD rats were randomly divided into normal control group,anxiety model group,depression model group,restraint stress group 3h group,restraint stress 6h group,chronic emotional stress group,modeling respectively.On the 14 th,21th and 28 th day after the modeling,the anxiety behavior of the rats was measured by the elevated cross maze and the scene fear test.The depressive behavior of the rats was measured by open field test and forced swimming test.The levels of 5-HT and DA in monoamine neurotransmitters were measured by Elisa kit.2.120 SD rats were randomly divided into normal control group,vehicle control group,anxiety model group,depression model group,restraint stress 6h group,corticosterone 40mg/kg group,restraint stress 6h + corticosterone 20 mg/kg group,restraint stress 6h +corticosterone 30 mg/kg group,restraint stress 6h + corticosterone 40 mg/kg group,modeling respectively.The anxiety and depressive behavior of rats were measured by elevated cross maze test,open field test and forced swimming test.The levels of CRH,ACTH and CORT in plasma were measured by Elisa kit.The contents of monoamine neurotransmitters in brain were detected by HPLC-ECD method.HE staining was used to detect the pathological damage of HPA axis tissues and the hippocampus,amygdala and prefrontal cortex.The expression of BDNF,NGF and NT-3 in the brain were detect by Western blotting.3.12 Chinese and Burma tree shrews were randomly divided into normal group,model group and drug group.The model group was modeled according to the previous model of anxious depression,the drug group was treated with venlafaxine(6 mg/kg)for 21 days while modeling.Autonomous activity score,sugar water preference experiment and Morris water maze was used to evaluate the behavior of tree shrews.The contents of CRH,ACTH and COR in the tree shrew plasma were determined by Elisa kit.The contents of monoamine neurotransmitters in the brain of the tree shrew were detected by HPLC-ECD.HE staining was used to observe the pathological damage of hippocampus,amygdala and hypothalamus in the tree shrew.Results:1.Optimized restraint stress 6h group as the best anxious depression psychological stress model.There was no obvious anxiety and depression in the restraint stress 3h group,and the contents of 5-HT and DA in the brain were no different from those in the control group.The anxiety behavior of the CES group was obvious,but it did not show depression in the forced swimming experiment.The contents of 5-HT and DA showed an increasing trend compared with the control group.The restraint stress 6h group began to show anxiety and depression at14 d,and the behavior was stable at 21 d,While the contents of 5-HT and DA in the brain decreased more obvious,can be used as the best anxious depression psychological stress model.2.The model of anxious depression animal model was established by chronic restraint stress 6h combined with corticosterone 30 mg/kg,and the multi-level evaluation system of this model was constructed.The time and frequency of open arm in the rats of 21 day restraint stress combined with corticosterone 30 mg/kg group,the frequency of independent activities in the open field were significantly different compared with the control group and depression group.The time of forced swimming was significantly higher than control group and anxiety group,and anxiety and depression were obvious.At the same time,compared with the control group,the contents of CRH,ACTH and CORT of rats plasma were significantly increased in the model group,HPA axis hyperthyroidism;The contents of 5-HT,NE and DA and the expression of neurotrophin BDNF,NGF and NT-3 were significantly decreased in the brain regions,the monoamines were unbalanced and neurotrophic deficiency.In addition,there were obvious damage in HPA axis and the brain regions in the model group observed from the pathological sections.3.A new animal model of anxious depression was successfully established by using near primate tree shrew.The autonomous activity score,sugar water partial eclipse degree and the learning and memory ability were significantly decreased in the model group.The contents of CRH,ACTH and COR in the model group were significantly higher than those in the normal group,the content of monoamine neurotransmitters in the brain decreased and the pathological damage was obvious.After treatment,the behavior of the tree shrew in the model group was improved,the contents of CRH and COR decreased,and the contents of 5-HT,NE and DA in the brain were improved to some extent,the 5-HT was the most significant.In line with the clinical treatment mechanism of the drug to enhance the 5-HT and NE concentration in the brain,and the predictive study confirmed that anxious depression model of tree shrew was established successfully.Conclusions:Above all,in this study,21 d restraint stress 6h combined with corticosterone 30 mg/kg could successfully establish an animal model of anxious depression was finally determined through optimized psychological stress model combined with corticosterone injection and the analysis of multiple concentrations and multiple time points.On the basis of this,a systematic evaluation system of the model was established from the aspects of animal behavior,blood biochemistry,histomorphology and molecular biology.And the tree shrew was further studied,a new animal model of anxious depression was established which is close to the human clinical.