Expression And Effects Of 5-HT System On Depression-like Behaviors In Epileptic Rats

【Purpose】In this study,epilepsy-associated depressive behaviours in the lithium chloride(Li Cl)-pilocarpine-induced post-status epilepticus(SE)rat model was established,and the distribution of 5-HTR subtypes in different parts of rat brain was explored.5-HT reuptake inhibitor(SSRIs)was used to investigate the effect of SSRIs on depressive behavior and epileptic discharge.【Methods】1.experimental animals were divided into groups: Lithium Chloride-Pilocarpine(Li Cl-pilocarpine)was injected intraperitoneally to induce status epilepticus in rats,and electrodes were implanted in rats after 3 weeks of successful epilepsy induction.All rats were subjected to five behavioral tests: Sucrose preference test(SPT),forced swimming test(FST),Tail suspension test(TST),Open field test(OPT)and Elevated-plus mazed test(EPM).SPT was performed once before and 4 weeks after molding.FST,TST,OPT and EPM were performed once at the end of observation after 4 weeks of modeling.According to the sugar consumption rate of SPT,immobility time of FST and immobility time of TST,the chronic epilepsy model of lithium chloride-pilocarpine rats was divided into epilepsy with no depressive behaviors(EWND group)and epilepsy with depressive behaviors(EWD group).2.Quantitative Real-time PCR(q PCR)was used to detect the expression changes of5-HT subtypes in olfactory,pre-cortex,striatum,amygdala,entorhinal cortex,hippocampus and midbrain.3.EEG monitoring: The electrodes were implanted in the third week after the successful establishment of the status epilepticus model,and after 7-10 days of postoperative recovery,the EEG of active rats was recorded by Power Lab system.4.Drug intervention: Depressive rats with epilepsy were screened out according to EEG and ethology,and escitalopram was injected intraperitoneally at 10mg/kg and20 mg/kg once a day for 2 weeks from the 5th week of modeling.The depressive behavior and epileptic seizures were observed by ethology and EEG.【Result】1.Compared with Control group,the behavioral results showed that in EP group,Sucro Rate of SPT was significantly reduced,immobility time of FST was significantly prolonged,climbing time was significantly reduced,central of OPT distance was significantly reduced,open arm stay time of EPM was significantly reduced,and other behavioral indicators had no difference.2.In EWD group,compared with Control group,the sugar consumption rate of SPT,climbing time of FST,immobility time of FST and TST,central distance of OPT,open arm residence time and times of entering open arm of EPM were significantly reduced.Compared with EWND group,the sugar water consumption rate of SPT in EWD group was significantly reduced,the immobility time of FST and TST was significantly increased,and the number of times of entering the open arm was significantly reduced.There was no difference in other behavioral indicators.3.The incidence of depression in chronic epilepsy model of lithium chloridepilocarpine rats is one third,and there is no significant difference in frequency and duration of epilepsy between EWND group and EWD group.4.Quantitative Real-time PCR(q PCR)was used to detect the expression of 5-HT,compared with the blank control group,the reslut showed that there were differences in the expression of olfactory,pre-cortex,entorhinal cortex,hippocampus,striatum,amygdala,and midbrain between EWND group and EWD group.5.Behavioral results showed that compared with those before drugging,the immobility time of SPT and FST were improved after giving 10mg/kg ESC,and the number of seizures and the duration of every seizure were significantly reduced.After 20mg/kg ESC,the immobility time of FST in rats was improved,the frequency of seizures increased obviously,the duration of single seizure had no significant difference,and the open arm residence time in EPM was significantly prolonged.【Conclusion】1.Chronic epilepsy model induced by lithium chloride-pilocarpine in rats is often accompanied by depression and anxiety-like behavior.2.There are differences in the distribution of 5-HTR subtypes in the brain of epilepsy rat with depressive behaviors in Li Cl-PILO.3.Inhibition of 5-HT reuptake on escitalopram can improve seizure and depression behavior of epileptic rats with depression,and its adverse reactions may be doserelated.