Establishment of a new depression rat model based on antagonistic relationship of brain neurotransmitter pairs / 中国病理生理杂志

ABSTRACT

AIM:To establish a new rat model of depression by the antagonistic relationship of antagonizing pairs of neurotransmitters in the brain.METHODS:Dopamine D1 receptor antagonist SCH23390 was injected into the hippocampus of the rats by microinjection at low, medium and high doses (1, 2 and 4 g/L) to establish a depression model.After modeling, the sucrose consumption, open-field and novelty suppressed feeding tests were used to evaluate the behaviors of the rats, and screen out the best modeling drug dose.The model of depressive rats was induced using the best modeling drug dose and the model rats were observed for 2 weeks.The stability of the model was evaluated by behavioral tests, and the contents of IL-1β and TNF-α in cerebrospinal fluid (CSF) were measured by ELISA to evaluate the safety of the model.The levels of the antagonizing pairs of neurotransmitters in the cerebral cortex and hippocampus were analyzed by the method of high-performance liquid chromatography-mass spectrometry (HPLC-MS), so as to evaluate the pathological characteristics of neurotransmitter imbalance in the brain of the model rats.RESULTS:After modeling, the rat weight, sucrose preference rate, and horizontal motion and vertical motion scores of open-field test were significantly decreased in eACh dose model group, and feeding latent periods of novelty suppressed feeding test were significantly increased, indicating a typical depressive behavior.The rats with the medium dose (2 g/L) of SCH23390 had the most significant depressive behavior.At 2 weeks after modeling, compared with the normal control group, the weight, sucrose preference rate, and horizontal motion and vertical motion scores in medium dose group were significantly decreased (P<0.01), while the feeding inhibition time was significantly increased (P<0.05).No significant difference in the content of IL-1β and TNF-α in the CSF of normal control group, blank control group and medium dose group was observed, indicating that the model did not cause obvious inflammatory injury, and the modeling method was safe.Compared with blank control group, the contents of 5-HT, NE and Glu in the left hippocampus of rats in medium dose group were significantly increased (P<0.01), and the content of DA and ACh showed decreasing trends.The contents of 5-HT, NE and Glu in the right hippocampus of the rats were significantly increased (P<0.05), and the contents of DA and ACh showed decreasing trends.The content of Glu in cerebral cortex was significantly increased (P<0.05), the contents of 5-HT and NE showed increasing trends, and the contents of DA and ACh showed decreasing trends, indicating that the model was basically consistent with the pathological features of neurotransmitter imbalance in the brain of depression.CONCLUSION:This method can successfully replicate the rat model of depression, which has the characteristics of typical and persistent symptoms, fast modeling, and safe and easy operation.Using the dosage of 2 g/L is more suitable.