Preliminary findings of a reduction of otoconia in the inner ear of adult rats prenatally exposed to phenytoin.
Pregnant Sprague-Dawley CD rats were administered phenytoin by gavage on days 7-18 of gestation in doses of 0 or 200 mg/kg. Following completion of a series of behavioral tests (20), progeny (18 months of age) were examined for otoconia in the vestibular labyrinth of the inner ear. None of the controls (N = 22) had reduced otoconia, while 23.3% of phenytoin-treated offspring (N = 43) had reductions. None of the controls, but 44.2% of phenytoin-treated offspring exhibited abnormal circling behavior during systematic examinations conducted in dry and swimming environments. Of the phenytoin-treated offspring exhibiting circling, 21.0% had reduced otoconia in either the utricle or saccule of one ear, while 25.0% of phenytoin-treated offspring not circling exhibited similar reductions. Conversely, 79% of phenytoin-treated offspring exhibiting circling did not exhibit any otoconial reductions. Thus, otoconial reduction cannot account for the majority of the cases of circling. The 21% vs. 25% otoconial reduction difference was not significant, however, when ratings of the magnitude of reduction were analyzed, circling offspring had significantly lower scores in their utricles than those not circling. More specifically, otoconial reduction in the right utricle and circling behavior were significantly related, although the number of concordant cases was small. Otoconial ratings did not differ for saccules. No differences in regional brain weights were found at the time of otoconial examination (560 days). The evidence provide preliminary support for the idea that prenatal exposure to phenytoin induces a reduction in otoconial crystals of the vestibular labyrinth in some of the exposed offspring, but it cannot account for most of the behavioral effects that have been observed in these offspring.
Minck
D R
DR
Institute for Developmental Research, Children's Hospital Research Foundation, Cincinnati, OH 45229-2899.
Erway
L C
LC
Vorhees
C V
CV
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology; D005260:Female; D010037:Otolithic Membrane / Q000187:drug effects* / Q000502:physiology; D010672:Phenytoin / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D012444:Saccule and Utricle / Q000187:drug effects*; D014722:Vestibule, Labyrinth / Q000187:drug effects
D010672:Phenytoin