RAT STRAIN-RELATED 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 abili ty of a neurobehavioral screening battery (functional observational ba ttery 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 influe nce of rat strain, and in LE males and females, to evaluate gender-rel ated 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-h ydroxide (intravenously). In general, the characteristic syndrome of t remor, Increased reactivity, and hyperactivity was observed; however, the magnitude and time course of these effects were much greater in F3 44 rats. Significant strain- but not gender-related differences were o btained when comparing TMT effects on different domains of neurologica l function. Comparisons of predosing data between male LE and F344 rat s, as well as between male and female LE rats, revealed significant di fferences in baseline values for about half of the measures of the tes t battery. These preexisting differences, however, could not account f or the observed dissimilarities in treatment effects Quantitative and qualitative differences were evident to a greater extent when comparin g LEs and F344s than between males and females. Therefore, conclusions based on these types of neurobehavioral screening data would be influ enced considerably more by the differences between rat strains.