Effect of Chaibei Zhixian Decoction on the expression of 5-HTT,5-HT1AR,5-HT2AR and DA2R in cerebral cortex and hippocampus of epilepsy-associated depression diseased rats
Objective This study aimed to investigate whether Chaibei Zhixian Decoction alleviate epilepsy-associated depression disease through the regulation of 5-HTT,5-HT1AR,5-HT2AR and DA2R in the cerebral cortex and hippocampus of lithium chloride(LiCl)-pilocarpine-induced epilepsy-associated depression rat model.Methods The lithium pilocarpine chronic temporal lobe epilepsy depression co-disease rat model was established.The rats were randomly divided into 6 groups:the control group,the model group,the positive drug group and the low,middle and high dose of Chaibei Zhixian Decoction groups.The rats were administered orally for 14 consecutive days,twice a day.After intervention,the behavioral monitoring of depression was carried out by sucrose preference test and forced swimming test.The levels of 5-HT and DA in rat cerebral cortex and hippocampus were detected by ELISA.The mRNA expression levels of5-HTT,5-HT1AR,5-HT2AR and DA2R genes in rat cerebral cortex and hippocampus were detected by real-time quantitative PCR.The method of western blotting was used to detect the protein expression levels of 5-HTT,5-HT1AR,5-HT2AR and DA2R in the cerebral cortex and hippocampus of rats.Results After Chaibei Zhixian Decoction intervention,compared with the model group,the sucrose consumption of the rats treated with middle and high doses of Chaibei Zhixian Decoction was significantly increased(P<0.01)and the immobility time was decreased(P<0.01).Compared with the model group,the levels of 5-HT and DA in the cortex in the middle(P<0.05)and high(P<0.01)doses of Chaibei Zhixian Decoction were increased.DA in the hippocampus of high doses were increased(P<0.01).Compared with the model group,5-HTT mRNA expression in the cerebral cortex was significantly decreased(P<0.01),while 5-HTT mRNA expression in the hippocampus was significantly increased(P<0.05).Furthermore,5-HT1A R mRNA expression in both cerebral cortex and hippocampus was significantly increased(P<0.05),and the protein expression level was consistent with the mRNA level.On the other hand,the mRNA and protein levels of-5HT2AR and DA2R did not change before and after drug treatment.Conclusion Chaibei Zhixian Decoction has the functions of down-regulation of 5-HTT in cerebral cortex,up-regulation of 5-HTT in hippocampus,and up-regulation of 5-HT1AR expression in cerebral cortex and hippocampus of rats with chronic temporal lobe epilepsy depression comorbidity,and improving depressive behavior.