Behavioral effects of prenatal d-amphetamine in rats: a parallel trial to the Collaborative Behavioral Teratology...

Pregnant Sprague-Dawley rats treated with 0, 0.5 or 2.0 mg/kg of d-amphetamine sulphate on days 12-15 of gestation or left untreated as part of the NCTR Collaborative Behavioral Teratology Study were assigned to either the Collaborative Study or Cincinnati Test protocol after birth. Offspring assigned to the Cincinnati test system were evaluated for growth, mortality, incisor eruption, eye opening, vaginal patency, surface righting, negative geotaxis, pivoting, auditory startle, olfactory orientation, swimming ontogeny, figure-8 activity, and complex water maze (Biel) problem solving. Amphetamine at both doses caused fewer offspring to be born per litter and reduced the proportion of males born in the 0.5 mg/kg group. Amphetamine produced no reliable effects on offspring growth as reflected by weight or survival. The 0.5 mg/kg amphetamine group showed delayed eye opening, but the 2.0 mg/kg group did not. Amphetamine produced no significant effects on other physical landmarks of development or on measures of behavioral performance except swimming ontogeny. Early swimming direction scores were significantly lower in the amphetamine groups compared to controls, but the effect was isolated; no other aspect of swimming was affected. It was concluded that at the doses and exposure period used here, d-amphetamine appears to be at best weakly behaviorally teratogenic using the Cincinnati test system. This finding is in general agreement with the results obtained with the same treatment regiment in the NCTR Collaborative Study. Both test systems appear comparable at correctly identifying the low level of behavioral teratogenicity of moderate doses of prenatal d-amphetamine.