SPONTANEOUS EPILEPTIFORM SEIZURES BUT INCREASED RESISTANCE TO KINDLEDSEIZURES IN A MUTANT SPRAGUE-DAWLEY RAT (MF MF)/

Approximately 30% of a breeding colony of Sprague-Dawley rats homozygo us for an autosomal recessive mutation mf (''mutilated foot'') associa ted with a peripheral sensory neuropathy have been found unexpectedly to suffer spontaneous epileptiform attacks. Seizures ranged from brief episodes of compulsive running to tonic-clonic convulsions lasting fo r up to 30 s, recurring at intervals of hours or days. EEG recordings during seizures showed high-voltage 8-10 Hz spike trains that abated o ver the ensuing 1-2 min. Interictal records were usually normal. Twice -daily kindling of the amygdala (200 mu A sinewave for 1.0 s) was unex pectedly ineffective. Most of the rats that had suffered spontaneous s eizures failed to develop kindled afterdischarges, even after 30 kindl ing stimulations. Other mf rats developed prolonged high-amplitude kin dled afterdischarges that were arrested at stage 2 and failed to evolv e into convulsive seizures. Hippocampal dentate granule cells of kindl ed mf rats, stained for zinc by Timm's method, showed significantly le ss messy fibre sprouting than wild-type Sprague-Dawley rats after the same number of kindled afterdischarges. A minority of the mp rats test ed (2 of 14) kindled normally. Auditory stimulation (n = 23) or strobo scopic flicker (n = 14) failed to elicit seizures or running fits in a ny mf rat. Peripheral neuropathy corresponding to that in the mf rat, with resistance to kindling and diminished messy fibre sprouting, have also been reported in transgenic mice with defective p75(NGFR) neurot rophin receptors. A homologous genetic defect in the rat could account for most of the features of the mf phenotype. (C) 1997 Elsevier Scien ce Inc.