Treatment of spontaneous and chemically induced EEG paroxysms in the Fischer-344 rat with traditional antiepileptic drugs or AED+CGP 35348 polytherapy

Abstract

Twenty-four Fischer-344 rats implanted with cortical electroencephalograph (EEG) electrodes were evaluated for frequency, duration, and mean duration (duration/frequency) of both spontaneous and chemically induced spike-and-wave discharges (SWDs) during earlier and later adulthood. Fischer-344 rats, exhibiting a low level of spontaneous SWDs during earlier adulthood, progressed to exhibit a significantly larger number and duration of SWDs during later adulthood. The convulsant trimethylolpropane phosphate (TMPP), known to antagonize the GABA A inhibitory system through blockade of the chloride channel, induced or increased SWDs in every rat tested. Spontaneous or chemically induced SWDs in Fischer-344 rats were eliminated or reduced by several drugs used to control human absence seizures. The gamma-aminobutyric acid (GABA) B antagonist CGP 35348 reduced spontaneous EEG paroxysms; CGP 35348 as a polytherapy with several traditional antiabsence treatments improved control of TMPP-induced seizures. It would appear that the Fischer-344 rat provides an excellent research alternative to use of genetically selected rodent strains for investigation of progression of absencelike epilepsy with aging, induction of SWDs by toxicant exposures, and treatment of spontaneous and chemically induced paroxysms.