The Effect Of 5-htp-microinjection In Mnr On The Release Of Extracellular Serotonin And Its Metabolite In Hippocampus Of Pilocarpine-induced Epileptic Rats.

【Object】To observe the dynamics of hippocampal release of 5-HT(serotonin) and 5-HIAA(5-hydroxyindoleacetic acid)in pilocarpine-induced temporal lobe epilepsy (TLE) after 5-HTP(5-hydroxytryptophan) microinjection in MnR(median raphe nucleus).【Method】The SD rats were divided into three groups:(1)the control group (KB) 8 rats were injected i.p.(intraperitoneally) with saline 0.9%;(2)the PILO group: 10 the rats were injected i.p with pilocarpine;(3)5-HTP group:10 pilocarpine-induced epileptic rats were microinjected in MnR with 5-HTP. The hippocampal extracellular(EC) fluid was collected by microdialysis during acute and chronic period of pilocarpine-induced epilepsy and the levels of 5-HTand 5-HIAA were measuered by high-performance liquid chromatography (HPLC) and electrochemistric determination(ECD).At last ,the peri-probe tissue was stained by H-E to check the position on which the probe was put was right or not,【Results】1.Behavior: The seizure of the rats could be divided into three phases: acute period,silent period and chronic period. During the chronic period ,there was a dramatic decrease of times of seizures in the 5-HTP group when compared with the PILO group (P<0.05).2. Electrocorticogram: (a) in the acute period (0-48h), a great quantity of intensive spike-wave was observed; (b) in the silent period (2-7days),α-wave was accompanied by a few low sharp-waves or Spike-and-slow-wave complex; (c) in the chronic period (7d-), spike-wave, Spike-and-slow-wave complex, sharp-waves and multiple spike-and-slow-wave complex were observed.During the chronic period,there was a sharp decrease of the frequency of seizures in the 5-HTP group when compared with the PILO group (P<0.05).3.The content of EC 5-HT and 5-HIAA in hippocampus: there was no difference in the basal lines of both 5-HT and 5-HIAA among the three groups; in the PILO group ,there was a great increase of 5-HT and 5-HIAA during the acute period(P <0.01), no change during silent period and a decrease during the chronic period(P <0.01) when compared with the KB group;during the chronic period ,there was a decrease f 5-HT and 5-HIAA when compared with the PILO group(P<0.05).4.There were 2 cases of dislocation and the data were discarded.【Conclusion】1. Pilocarpine-induced epilepsy is an ideal model to investigate the basic epileptic mechanisms involving the hippocampus during the acute and chronic period.2 Combined with HPLC, microdialysis can provide near real-time information on the time-dependent concentration changes of 5-HT and 5-HIAA in the EC fluid in vivo.3. 5-HTP-microinjection in MnR may protect against seizures through improving the EC level of 5-HT in hippocampus.