Methodological considerations in neurobehavioral teratology.

Neurobehavioral teratology is a rapidly expanding field benefitting from recent advances in neurobiology and behavior and from the increasing availability of compounds with specific pharmacological actions. There is evidence that data derived from animal studies are clinically pertinent and hence animal studies are useful in extending clinical findings, in anticipating consequences of early drug exposure and, by determining the underlying neural mechanisms, in developing therapeutic approaches. However, the usefulness of animal studies crucially depends on the reliability and sensitivity of the methods used. We highlight the importance of appropriate selection of the route, dose, frequency, duration and timing of drug administration. We also emphasize the importance of not confounding treatment with litter effects and suggest that either the litter be used as the unit of analysis, or that each litter contribute only one pup to each test condition. We discuss the question of the time of testing and of testing, not only under baseline conditions, but also in conditions in which the offspring are exposed to stressful, pharmacological or cognitive challenges. We hope that future studies will benefit from these considerations and avoid the methodological weaknesses that beset some of the early studies in this field.