Rat strain- and gender-related differences in neurobehavioral screening: acute trimethyltin neurotoxicity

Trimethyltin (TMT) produces unique pathological and behavioral changes after a single dose. In this study, TMT was used to examine the ability of a neurobehavioral screening battery (functional observational battery and motor activity) to characterize these behavioral changes in rats. The behavioral profile of TMT was obtained using these tests in male Long-Evans (LE) and Fischer 344 (F344) rats, to assess the influence of rat strain, and in LE males and females to evaluate gender-related differences. All rats were tested before dosing and again at 1, 7, 21, and 42 d after a single dose of either 0, 4, 6, or 8 mg/kg TMT-hydroxide (intravenously). In general, the characteristic syndrome of tremor, increased reactivity, and hyperactivity was observed; however, the magnitude and time course of these effects were much greater in F344 rats. Significant strain- but not gender-related differences were obtained when comparing TMT effects on different domains of neurological function. Comparisons of predosing data between male LE and F344 rats, as well as between male and female LE rats, revealed significant differences in baseline values for about half of the measures of the test battery. These preexisting differences, however, could not account for the observed dissimilarities in treatment effects. Quantitative and qualitative differences were evident to a greater extent when comparing LEs and F344s than between males and females. Therefore, conclusions based on these types of neurobehavioral screening data would be influenced considerably more by the differences between rat strains.