Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol treatment.
Methylazoxymethanol acetate (MAMac) is a potent teratogenic agent which can produce ectopic cell placement in developing rat brains. In the present study, we evaluated (i) whether prenatal exposure to MAMac results in a lowered seizure threshold to flurothyl and (ii) if there is a correlation between the number of ectopic cells in MAMac-exposed hippocampus and flurothyl-induced seizure latency. In 60 day old (P60) rats exposed to MAMac in utero, the latencies to myoclonic jerk (173 +/- 2.3 s) and forelimb clonus (215 +/- 4.6 s) were significantly shorter than those of controls (200 +/- 6.9 s and 238 +/- 8.8 s, respectively). MAMac also increased the proportion of flurothyl-treated rats that progressed from bilateral forelimb clonus to generalized tonic-clonic seizures (control: 33%; MAMac: 91%). Shorter seizure latencies were associated with an increased number of ectopic pyramidal cells in region CA1/CA2. These results suggest seizure susceptibility is enhanced in an animal model (MAMac) characterized by abnormal neuronal migration.
Baraban
S C
SC
Department of Neurological Surgery/Physiology, University of Washington, Seattle 98195, USA. bara@tt.washington.edu
Schwartzkroin
P A
PA
D000818:Animals; D003292:Convulsants / Q000494:pharmacology*; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D005481:Flurothyl / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives*; D051379:Mice; D009207:Myoclonus / Q000139:chemically induced / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology; D013723:Teratogens
D003292:Convulsants; D013723:Teratogens; D008746:Methylazoxymethanol Acetate; D005481:Flurothyl; C030667:methylazoxymethanol