Testing strategies in behavioral teratology: IV. Review and general conclusions

Three laboratories collaborated to evaluate and compare different test concepts to be used for routine testing in behavioral teratology. Rat dams were treated orally with methylmercury starting two weeks prior to pairing until weaning of their offspring. In the first laboratory, the usual reproduction parameters were assessed in the dams, and all offspring (96-103 per group) were subjected to a routine developmental and behavioral test battery. After termination of the tests a random selection of these animals was further tested by multiparametric automated techniques in the other two laboratories. In one of these laboratories 12-13 males and females per group (one of each per litter) were tested in a visual discrimination reversal schedule, using nose-poking as operand. In the other laboratory the free behavioral of eight randomly selected males per dose group was studied in a wheel-shaped activity monitor with respect to locomotion magnitude and structure. In the same laboratory eight other males per group were trained in a discrete trial spatial alternation schedule, using lever press as operand. Both the developmental and behavioral testing battery as well as the automated techniques showed some significant effects in the offspring even at the low dose, where no reproduction effects had been noted. However, whereas the testing battery results were of unspecific nature, results of the automated techniques gave precise and specific information. In order to obtain optimal information, it is proposed to combine both approaches for routine testing. This combination could be achieved by using a balanced testing battery in young pups followed by an appropriate operant conditioning schedule in selected young adults.