Ethological Approaches in Pharmacology: Prenatal Antioxidant Supplementation during Intrauterine Hypoxia in Rats and Behavioral Effects of Acetylcholinesterase Inhibitors in Mice

The experimental findings presented provide insight into the evaluation of behavioral effects, an important component for in vivo screening of drugs or toxic compounds in experimental animals. In the first set of experiments, we studied the effect of chronic intrauterine hypoxia produced by phenytoin on pre- and postnatal development of the rat offspring. Surprisingly, we found that high doses of VitE in pregnancy, which should be protective, appear to involve a risk to the developing rat fetus. In the second set of experiments, we studied behavioral changes after AChE inhibition. Subchronic exposure to low-levels of sarin combined with chronic shaker stress caused delayed changes in behavioral and endocrine parameters. With the methods presented in this book we were able to detect an embryo-fetal toxic potential of PHT and to point out the risk of prenatal supplementation with high doses of VitE to the developing rat fetus. The behavioral methods also enabled us to detect late consequences of exposure to anti-ChE, and particularly to sarin in combination with stress, providing a possible model of Gulf War Syndrome.