Aspects of Neurobehavioral Teratology

There are a number of theoretical and practical factors that have to be taken into account in behavioral teratology. A complete overview can be found in literature (refs. 62, 109, 167-169). In this section only some of the most important problems are discussed. 

In case of prenatal treatment, care should be taken that pups are fostered appropriately (ref. 169). Otherwise, postnatal effects of changes of maternal behavior resulting from the treatment might be confounded with prenatal effects of fetal exposure to chemicals. Changes in pup-dam interactions, caused by effects of postnatal treatments on either the dam or the pup, may lead to indirect teratogenic effects. It is difficult to distinguish such effects from direct teratogenic effects. Furthermore, exposure of dam and fetus or pup to chemicals may cause indirect effects because of induction of 

Oose-effect relations in neurobehavioral teratology may be complex. For instance, high doses of naloxone may stimulate certain aspects of development, while lower doses have the opposite effect (see below). A prenatal dose of 10 mg/kg methadoneresulted in a larger increase in activity of rats on postnatal days 17 and 22 than a dose of 15 mg/kg (ref. 49). This type of dose-effect relations is very common in psychopharmacology, and probably also in neurobehavioral toxicology. Careful choice of dose range is necessary since ineffectiveness of a certain dose level does not always mean that all lower doses can be assumed to have no effect. 

When making a choice of test situations, some investigators are biased by the effects of the tested substance in adulthood. Based on this knowledge, it is possible to formulate and test a specific hypothesis about aspects of brain and behavioral development that are expected to be affected. For instance, haloperidol can be expected to alter development of the dopamine system and motor activity, whereas clonidine can be expected to affect development of the catecholamine system and REM sleep. 

A quite different approach is adopted by investigators interested in all possible toxic effects, independent of the effects expected on the basis of current knowledge. Often no specific hypothesis is possible in case of screening for possible adverse effects of chemicals on development. Moreover, it is essential to take into account that unexpected effects might occur. Therefore, it is necessary to investigate effects on a wide range of behaviors in order to decrease the chance of missing an important effect. 

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