Ahi1/Cend1 Pathway Mediates The Antidepressant Effect Of Meptazinol

Background:Depression is a common psychiatric disorder.The main clinical symptoms are depression,slow thinking,lack of pleasure,decline of volitional activity,cognitive impairment and somatic symptoms.More serious cases may have suicide attempts or behavior.At present,there are many kinds of commonly used antidepressants in clinic,and there is no ideal antidepressant.It has been reported that in clinic,about 50%of patients with chronic pain will have depression and other affective disorders,and the depressive symptoms will be improved after the treatment of analgesics such as meptazinol(Mep).Therefore,this study mainly explores the antidepressant effect of meptazinol in primary depression and its main mechanism.Methods:In this study,ICR mice were used to induce the model of depression with spatial behavior restriction;forced swimming and tail suspension tests were used to detect depression-like behavioral changes in mice;Western blot was used to detect the changes in the content of related proteins;and Q-PCR was used to detect the changes in the level of related genes;Immunofluorescence staining was used to detect the changes of cell proliferation.Results:After the depression model was established by spatial behavior restriction,the depression-like behavior was detected in the forced swimming test and tail suspension test.After three weeks of continuous treatment with meptazinol(10mg/kg),the immobility time of TST and FST in the model mice decreased significantly,and the depression-like behavior was alleviated,suggesting that meptazinol has antidepressant effect.Western blot analysis showed that the protein level of Ahil was significantly elevated and the expression level of Ahi1 was also significantly elevated in the hippocampus of mice after treatment with meptazinol,but meptazinol did not improve the depression-like behavior of mice in the Ahil and Cendl knockout mice,and in the absence of Ahi1,the protein level of Cendl in the nucleus of hippocampus of mice was significantly elevated.The content of Cendl in the nucleus of the hippocampus increased significantly after two weeks of administration of meptazinol(lOmg/kg)in WT mice,Immunofluorescence staining showed that the number of BrdU-positive cells in WT mice treated with meptazinol increased significantly after one week of continuous intraperitoneal injection of BrdU(50mg/kg).Conclusions:Meptazinol has antidepressant effect.It can exert its antidepressant effect through Ahi/Cendl pathway and provide a new drug choice for clinical treatment of depression.