Effects of prenatal diphenylhydantoin treatment on reproductive outcome, development, and behavior in rats

Protective role of endogenous catalase in baseline and phenytoin-enhanced neurodevelopmental and behavioral deficits initiated in utero and in aged mice

“…This is consistent with the protection observed with enhanced levels of catalase in the hCat pups. Previous studies showed a delay in surface righting in rats following in utero phenytoin exposure [12], but no such differences were seen in this study, similar to another report in rats [14], possibly due to the relatively low dose of phenytoin used to avoid neonatal death.…”

“…This study tested neonates on the time-specific development of reflexive and spontaneous behaviors that are typical in rodents, and reported to be sensitive to a variety of insults such as in utero exposure to phenytoin [12][13][14]. Deviation in the developmental course of these behaviors is suggestive of alterations within an organism [36], although the precise relationship between developmental insult and behavioral abnormalities is not fully understood.…”

“…Subsequent studies in pregnant rats using phenytoin doses of 50-200 mg/kg by gavage also observed a delay in the development of the air righting reflex [9,[11][12][13]. Numerous other neurodevelopmental deficiencies, such as impaired startle reflex, impaired maze performance and abnormal circling tendency, have been described in rat offspring exposed in utero to phenytoin [9,[11][12][13][14]. Gender may exert a modulatory influence, as phenytoin exposure caused a greater delay in air righting and acceleration in the negative geotaxis test in females, while a greater acceleration in olfactory orientation was seen in males [13].…”

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

“…A large number of studies have shown that phenytoin can be neurobehaviorally teratogenic in animals at doses below those producing malformations (Table 5) (Elmazar and Sullivan, 1981;Vorhees, 1987b;Vorhees and Minck, 1989;Minck et al, 1991;Pizzi and Jersey, 1992). A broad range of behavioral deficits has been found in these animals, most notably a substantial difficulty with spatial learning tasks, including spontaneous alternation, the Biel or Cincinnati water mazes, and the Morris and radial eight-arm mazes (Vorhees and Minck, 1989;Weisenburger et al, 1990;McCartney et al, 1999;Schilling et al, 1999).…”

Delayed Developmental Effects Following Prenatal Exposure to Drugs

“…Treatment of pregnant rats with nonmalforming doses of phenytoin (dose range 100-200 mg/kg, which produce plasma drug levels in the human therapeutic range) on days 7-18 of gestation induced in the offspring hyperactivity in the early phases of development, at adolescence and at adulthood, delayed righting reflex ontogeny, delayed swimming ontogeny, decreased habituation to a novel test environment, reduced responding to tactile stimulation, and deficits in maze learning and memory and abnormal circling behavior [111][112][113][114][115][116][117][118][119]. As for the mechanisms by which phenytoin induces its long-lasting behavioral effects, they are unclear.…”