Behavioral assessment of aging in male Fischer 344 and brown Norway rat strains and their F1 hybrid.

Male Fischer-344 (F344) and Brown Norway (BN) rats 7-, 13-, and 24-month-old and their F344 x BN hybrid (F1) 7-, 13-, 24- and 31-month-old were tested in a behavioral battery (15-min and 24-h locomotor activity, inclined screen, rod suspension, rotorod, shock-motivated learning in a straight runway and 14-unit T maze). Necropsy was performed 3 days later and the results rated for pathology (i.e., severity of lesions observed). Age-related performance declines were observed in all behavioral tests except 15-min locomotor activity. Strain effects were observed in 15-min (BN more active than F344 and F1) and 24-h locomotor activity test (F344 more active than BN and F1 strains); rotorod performance (F344 fell more than BN and F1); and in all measures [errors (E), runtime (RT)], shock frequency (SF), and duration (SD)] in the 14-unit T maze (F344 worse than BN, BN worse than F1). T maze performance of 31-month-old F1 rats was deficient in RT, SD, and SF but E performance was equivalent to that of 7-month-old F1 rats. In a second experiment, only 7- and 31-month-old F1 rats were tested in the 14-unit T maze and the results obtained in Experiment 1 were replicated. Gross necropsy revealed age and strain effects in the number of lesions observed and the mean ratings of pathology. The 24-month-old F344 rats exhibited the greatest number of lesions and had the highest ratings (generally observed as chronic nephrosis and enlarged spleens characteristic of mononuclear cell leukemia). BN rats exhibited a high incidence of hydronephrosis at all age levels. While experiencing less obvious pathology, F1 rats experienced a significant number of lesions in the 31-month-old group. Pathology ratings correlated with behavioral performance but only for a few tests (e.g., SD and RT in 14 unit T maze in 24-month-old F344). Thus, behavioral performance declined with age and the battery of tests differentiated between the strains tested (in general, F344 worse than BN; BN worse than F1). The correlation of pathology ratings at gross necropsy with behavior did not appear to be systematic, suggesting that morbidity was not responsible for the age-related performance declines. However, more extensive evaluation of the relationship of age-related changes in health status to behavior with larger samples of rats is suggested.