5-hydroxy-indole Aectic Acid Levels In Hippocampus And Frontal Cortex Of Rats With Epilepsy Kindled By Pentylenetetrazole And The Effect Of Fluoxetine On Their Epilepetic Activity

Objective: The aim of this study was to investigate the involvement ofserotonergic systems as epileptogenesis modulator by measuring the concentrations of5-hydroxytryptamine (5-HT) and its metabolites 5-hydroxyindoleacetic acid (5-HIAA)in defferent brain area (hippocampus and frontal cortex )of epileptic rats induced bypentylenetetrazol (PTZ). And also to assess the effects of different dose acutefluoxetine pre-treatment on the pentylenetetrazol kinded models to shape a model oftreatment in epileptic patients with depressive syndrome and. explore if fluoxetine canbe a assistant drug in treatment of epilepsy.Methods: 8 Wistar rats were selected randomly from 60 Wistar rats as a normalcontrol group. The rest rats were injected intraperitoneally (injectedintraperitoneally, ip) PTZ (35mg/kg) every other day to establish chronic PTZ-kindlingmodel..After kindling models were established (n=46), Rats were divided randomlycompletely into five groups: fluoxetine (1.10.20 mg/kg) group, PTZ group. Rats wererespectively pretreated with fluoxetine(1.10.20mg/kg) and 0.9% salineintraperitoneally. 60min later, treated with a single dose PTZ (35mg/kg,ip); modelcontrol group: Two step were both treated with 0.9% saline(2ml/mg)..Immediatelyafter PTZ administrations, seizure behavioural changes were observed during 60minafter the PTZ treatment. The seizure latency,duration, intensity of the seizures andcase of tetanic convulsion were observed and scored. The seizure intensity wasobserved with Ono's method and compared with those of the PTZ treatment. Normalcontrol group(n=8), PTZ group, model control group were killed by decapitation60min after the treatment and brains were dissected on ice to remove frontal cortexand hippocampus. The levels of 5-hydroxytryptamine (5-HT) and its metabolites 5-hydroxyindoleacetic acid (5-HIAA) were determined by flurospectrophotometry.Resoult: Compared with PTZ group There was a significant increase in the latencyof seizure activity, decreased average Ono's stage and percentage of tetanic-convulsion in the fluoxetine-treated (10 and 20mgkg ip) group (P＜0.05or P＜0.01).These were no significant different between the PTZ group and the fluoxetine-treated (1mgkg) group (P＞005). Furthermore, Different was significant betweenFluoxetine(20mg/kg)-treated group and fluoxetine-treated(10mgkg) group in thelatency,average Ono's stage of seizure (P＜0.05). In relation to seizure activityduration, no significant different were found.among four groups (P＞005).2 For the hippocampus determinations, 5-HT concentrations in model group andPTZ group both were significantly lower than control group (P＜0.05 or P＜0.01); Theconcentrations of 5-HT were significantly lower in PTZ groups compared with modelgroup (P＜0.05). 5-HIAA in hippocampus of PTZ group was lower than normalcontrol group (P＜0.05).whereas, In relation to frontal cortex determinations, 5-HTconcentrations of model and PTZ group were higher than control group (P＜0.05 orP＜0.01). 5-HT concentrations of PTZ group were higher than that of model group(P＜0.05). The contents of 5-HIAA of three groups have no significant different(P＞0.05).Conclosion: 1. These results indicate that 5-hydroxytryptamine is a modulator ofepileptogenesis; And its effect on seizure activity depend on the brain area studied.In hippocampus it may play an inhibitory role, on the contrary, it may show aexcitatory effect.in frontal cortex. Different mechanisms involved need to be furtherstudied.2.fluoxetine (10,20mg/kg ip) can significantly prolonged the latency,decreased percentage of titanic-convulsion, and attenuates intensity of thePTZ-induced seizures in rats. This inhibition shows to be dose-dependently. Ourresults suggest fluoxetine may have antiepileptic activity. Administration of this drugin epileptic patients with depressive disorder seems to be safe. It has a therapeuticpotential in the treatment of seizures in epileptic patients with depression.. Furtherstudies need to confirm the anticonvulsant effect of it. including the use of morerelevant models of epilepsy like kindling models.