Long-term effects of continual intake of phenobarbital on the spontaneously epileptic rat.

Spontaneously epileptic rats (SER) are a double mutant (zi/zi, tm/tm) spontaneously exhibiting both tonic and absence-like seizures. We examined the long-term effects of continual intake of phenobarbital (PB) on SER as a method of assessing long-term evaluation of antiepileptic drugs (AEDs). Food pellets containing 0.1% PB were given ad libitum from 7 weeks of age. Plasma PB level was maintained at 30-70 micrograms/ml after age 11 weeks. Tonic seizures were inhibited markedly in rats that received PB until age 15-16 weeks, but thereafter the inhibitory effects of PB gradually decreased. An increase of body weight and prolongation of survival were also noted in SER that received PB. Cortical and hippocampal EEG of SER were recorded with chronically implanted electrodes from 11 weeks of age pre-PB and 3, 7, and 14 days post-PB intake. These animals exhibit absence-like seizures characterized by sudden appearance of 5-7-Hz spike-wave-like complexes on EEG concomitant with immobility and staring. The seizures were not affected until age 13 weeks (2 weeks after intake of PB), although tonic seizures were inhibited. SER are considered a useful model for evaluating the long-term effects of AEDs.