The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: behavior and metabolism

Abstract

This work describes a novel epilepsy model, combining pentylenetetrazole (PTZ) kindling with the senescence-accelerated mouse P8 (SAMP8) a model for aging. The 2- and 8-month-old SAMP8 mice were treated with PTZ, phenobarbital plus PTZ or saline every 48 h during a period of 40 days. Both 2- and 8-month-old PTZ-kindled mice showed a behavioral pattern that was very similar to severe chronic epilepsy with secondary generalized seizures. Two out of six 8-month-old animals died in the PTZ group. Interestingly, atypical absence seizures were limited to the 8-month-old PTZ group. Furthermore, 8-month-old mice were more sensitive to the sedative effect of phenobarbital. The concentrations of several amino acids were examined by HPLC. Lower levels of amino acids were found in the 8-month-old compared to the 2-month-old control animals. No biochemical changes were observed between the groups of 2-month-old animals, while in the 8-month-old animals both treatment groups showed significantly higher concentrations of GABA, glutamine and glutathione. Thus, it could be shown that cerebral metabolism of 8-month-old SAMP8 mice was more sensitive to PTZ and phenobarbital than metabolism of 2-month-old mice. Furthermore, it is suggested that glutamate metabolism in brains of 8-month-old SAMP8 mice is altered and that excessive glutamate is transformed, in considerable amounts, into glutamate related metabolites, possibly in astrocytes.