d-Amphetamine as a behavioral teratogen: effects depend on dose, sex, age and task

Reports on the behavioral effects of prenatal exposure to d-amphetamine in rodents are inconsistent. Activity levels have been variously reported to increase, decrease, or show no change (as in the Collaborative Study) following such exposure. As a follow-up to the Collaborative Behavioral Teratology Study, 3 experiments have been conducted at the NCTR to examine the behavioral teratogenicity of this compound following SC dosing on days 12-15 of gestation. A higher dosage (3 mg/kg) was included and evaluations involved tasks used in the Collaborative Behavioral Teratology Study (startle, figure-8 activity) and other tasks not previously undertaken at the NCTR (short-term reactivity to novel open fields, intake of sweetened solutions). Activity measures gave especially mixed results. There was no effect of prenatal exposure, even at 3 mg/kg, upon longer-term activity, before or after amphetamine challenge, in figure-8 mazes or rectangular photocell chambers, at postnatal days (PND) 47 or 120. In one experiment, changes in reactivity to brief exposure to an open field daily over 3 days were seen in higher dosage PND 135 males but not females, while higher dosage females but not males showed lowered emergence latencies at this age. In a second experiment, no exposure-related changes were seen in reactivity to an open field in offspring of either sex at PND 47 or 70. Auditory startle amplitude showed complex dose effects in these two experiments. Females exposed to 3 mg/kg had elevated startle amplitude at PNDs 47 and 120, but not at PND 19. Males in the 3 mg/kg group had elevated startle at PND 19, but not thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)