PMID- 15734280
OWN - NLM
STAT- MEDLINE
DCOM- 20050509
LR  - 20191210
IS  - 0892-0362 (Print)
IS  - 0892-0362 (Linking)
VI  - 27
IP  - 2
DP  - 2005 Mar-Apr
TI  - Permanent motor activity and learning disorders induced by exposure to phenytoin 
      during gestation and early infancy in the rat.
PG  - 299-310
AB  - Experimental models and clinical data indicate that the incidence of motor and 
      learning disorders may be increased in children of epileptic mothers taking 
      phenytoin (PHT) during pregnancy. There is little data on the vulnerability of 
      infants to PHT-induced long-term behavioral toxicity after gestational or early 
      life exposure (i.e., infantile convulsion therapy). We examined the persistence 
      of alterations in circling behavior induced by exposure to PHT during gestation, 
      infancy, or both. Pregnant Sprague-Dawley rats were injected i.p. with saline 
      (SAL) or PHT (30 mg/kg/day) during gestational days (GD) 10-18. The offspring 
      were then administered (i.p.) SAL or PHT (60 mg/kg/day) during postnatal days 
      (PD) 13-23. Afterward, Circling Training tests were performed at three time 
      points. At PD40 and PD80, the clockwise direction of circling was reinforced. At 
      PD150, counterclockwise circling was rewarded instead. At PD40, all PHT-treated 
      groups demonstrated increased circling velocities compared to saline-treated 
      controls. Higher spatial error rates for direction of circling were also observed 
      in gestation-only and infancy-only exposures. At PD80, groups exposed during 
      gestation had higher circling velocities than control or infancy-only exposed 
      groups. At PD150, increases in circling velocity were apparent for the reverse 
      learning task in groups exposed during gestation. These results indicate that 
      early postnatal exposure to PHT may exacerbate the known long-term behavioral 
      effects of gestational exposure.
FAU - Wolansky, Marcelo Javier
AU  - Wolansky MJ
AD  - Interdisciplinary Project on Neuroteratology, Departamento de Biodiversidad y 
      Biologia Experimental, Facultad de Ciencias Exactas y Naturales, Ciudad 
      Universitaria, Universidad de Buenos Aires, Buenos Aires, Argentina. 
      wolansky.marcelo@epa.gov
FAU - Azcurra, Julio Marcos
AU  - Azcurra JM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 0 (Anticonvulsants)
RN  - 6158TKW0C5 (Phenytoin)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Animals, Newborn
MH  - Anticonvulsants/*toxicity
MH  - Behavior, Animal/drug effects
MH  - Birth Weight/drug effects
MH  - Female
MH  - Learning Disabilities/*chemically induced
MH  - Litter Size/drug effects
MH  - Maternal Behavior/drug effects
MH  - Motor Activity/*drug effects
MH  - Phenytoin/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reversal Learning/drug effects
MH  - Spatial Behavior/drug effects
MH  - Stereotyped Behavior/drug effects
MH  - Survival Analysis
EDAT- 2005/03/01 09:00
MHDA- 2005/05/10 09:00
CRDT- 2005/03/01 09:00
PHST- 2004/09/02 00:00 [received]
PHST- 2004/12/27 00:00 [revised]
PHST- 2004/12/28 00:00 [accepted]
PHST- 2005/03/01 09:00 [pubmed]
PHST- 2005/05/10 09:00 [medline]
PHST- 2005/03/01 09:00 [entrez]
AID - S0892-0362(05)00002-4 [pii]
AID - 10.1016/j.ntt.2004.12.006 [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 2005 Mar-Apr;27(2):299-310. doi: 10.1016/j.ntt.2004.12.006.