INVESTIGATIONS OF FETAL DEVELOPMENT MODELS FOR PRENATAL DRUG EXPOSUREAND SCHIZOPHRENIA - PRENATAL D-AMPHETAMINE EFFECTS UPON EARLY AND LATE JUVENILE BEHAVIOR IN THE RAT

Recent evidence suggests that mid-pregnancy is a critical period for p roduction of fetal abnormalities that cause behavioral and neuropathol ogical changes in adult offspring. The present experiments provide an animal model of these effects by treating pregnant Sprague-Dawley rats during gestational days 11-14 with d-amphetamine (AM). Offspring were tested for neurological signs, foraging activity, reversal learning, and sensitivity to amphetamine challenge. In the Early Juvenile period , postnatal days (PND) 20-30, female AM offspring initially showed red uctions in rearing, holepoking, and midfield activity. On later trials , and as young adults, AM females showed signs of locomotor hyperactiv ity despite continued poor foraging efficiency, and were also more sen sitive to a 1.0 mg/kg d-amphetamine challenge. AM males showed initial ly slower and more perseverative responding than controls, but then de veloped excessive response switching. These changes continued during t ests for Retention, Reversal, and Extinction in the Late Juvenile/Earl y Adult stage (PND 50-90), when both AM-exposed sexes showed increased eating time, significantly more perseverative lateral turning prefere nce (right or left), and slower reversal learning than controls. Behav ioral data were consistent with aberrations in thalamo-frontal and mes olimbic/nigrostriatal projection systems that have been reported in AM animals and which are also affected by maternal drug abuse and schizo phrenia.