Strain Differences in the Effect of Long-term Treatment with Melatonin on Kainic Acid-induced Status Epilepticus, Oxidative Stress and the Expression of Heat Shock Proteins

The present study compared the effects of subchronic treatment with melatonin administered via subcutaneous osmotic minipumps for 14 days (10 mg/kg per day) on kainic acivd (KA)-induced status epilepticus, oxidative stress and expression of heat shock protein (HSP) 70 in the frontal cortex and hippocampus between normotensive Wistar rats and spontaneously hypertensive rats (SHRs). SHRs showed increased lipid peroxidation (LP) in the cortex and hippocampus and decreased cytosolic superoxide dismutase (SOD/CuZn) production in the cortex compared to Wistar rats. Long-lasting seizures induced by KA (12 mg/kg, i.p.) were accompanied by increased LP and expression of HSP 70 in the hippocampus of the two strains and increased SOD/CuZn production in the frontal cortex of SHRs. Pretreatment with melatonin failed to supress the KA-induced SE in the two strains though the latency for seizure onset was significantly increased in SHRs. The increased LP induced by KA in the hippocampus was attenuated by melatonin pretreatment both in Wistar rats and SHRs. The increase of SOD/CuZn and mitochondrial SOD/Mn production was strainand area-specific in melatoninKA treated groups. Melatonin prevented the KA-induced increased expression of HSP 70 in the hippocampus of KA-treated Wistar rats. The study, suggest that the potential efficacy of melatonin pretreatment on SE-induced oxidative stress and neurotoxicity is strainand area-specific.