Effects of amphetamine on rat embryos developing in vitro.

Wistar rat embryos were explanted on Day 10.5 of gestation and exposed in vitro to amphetamine (AMP) at concentrations of 0.1, 0.4, 0.8, 1.2, or 1.6 mM for 24 h, and the direct dysmorphogenic effects of the drug on the embryos were examined by comparisons with a control group. The viability of the cultured embryos was not affected by the AMP treatment. The yolk sac diameter was reduced at AMP concentrations of 1.2 and 1.6 mM. The crown-rump length, the somite number, and the protein content of the embryos were decreased significantly at these two doses, as was the developmental score. The frequency of malformed embryos was increased significantly at the two highest concentrations. The malformations induced in treated embryos included microcephaly, neural tube defects, incomplete rotation of the body axis, and tortuous spinal cord. Abnormal histologic changes, such as derangement and necrosis of the neuroepithelial tissue, were observed in the embryos exposed to the two highest concentrations of the drug. The observed embryotoxic effects appeared to depend on the AMP concentration. Our results demonstrated the direct embryotoxic effects of AMP on rats. The direct dysmorphogenic effect of AMP might be weaker than that of methamphetamine.