Detection limits of different approaches in behavioral teratology, and correlation of effects with neurochemical parameters.

Five laboratories collaborated in the evaluation of detection limits of different testing concepts in behavioral teratology. In one laboratory, rat dams were treated by gavage with five doses of methylmercury (0.0, 0.25, 0.05, 0.5, and 5.0 mg/kg/day). The treatment period was restricted to days 6 to 9 of gestation. The usual reproduction parameters were assessed in the dams. The offspring (88-99 per group) were subjected to a routine developmental and behavioral testing battery. After completion of these tests, random samples of the animals were further investigated in four other laboratories using the following techniques: auditory startle habituation, visual discrimination and figure-8 activity monitor; wheel-shaped activity monitor and spatial alternation operant conditioning; two-compartment locomotor activity, passive avoidance and male ultrasonic vocalization during sexual behavior; assays of the weight of different brain areas, their glial fibrillary acidic (GFA) protein and S-100 protein concentration. The following dose-dependent effects were noted in ascending dose sensitivity order: delayed vaginal opening; increased and more variable passiveness in spatial alternation; impaired swimming behavior, increased GFA protein concentration in the cerebellar vermis; increased auditory startle amplitude, decreased intertrial interval pokes in the visual discrimination test, increased percentage of visits in passive area of figure-8 activity monitor, increased path iteration frequencies and decreased local activity in the wheel-shaped activity monitor, decreased locomotor activity in the two-compartment monitor, increased cerebellar vermis weight, and decreased S-100 protein in the hippocampus. Therefore, this study showed comparable sensitivities for the behavioral testing battery, for some automated multiparametric test systems and for the neurochemical assays.