Comparison of Different Cognitive Rat Models of Human Aging

Multiple rat strains have been used for behavioral tests of cognitive function. This chapter will discuss the advantages and disadvantages of commonly used rat strains in aging studies and offer insight concerning the ability to generalize behavioral data. Differences of the outbred and inbred strains in the behavioral tasks, middle-aged data, and life expectancy will be discussed comprehensively to facilitate the design of future experiments to maximize comparability across rat strains. Aged Long Evans (LE) rats have been thoroughly characterized using the Gallagher spatial learning protocol in the water maze, performance of which depends on the integrity of the medial temporal lobe. However, due to availability from the National Institute of Aging, much of the reported aging studies in rats use the Fischer 344 (F344), Brown Norway (BN), or the F344 x BN hybrid strains. Recently, the performance of aged F344 and F344xBN hybrid strains has been examined using the Gallagher protocol. This chapter will compare the performance of each of these strains with the Long Evans rats using the same water maze protocol. Additionally, middle-aged cohorts have been introduced into experiments with the hope of increasing the sensitivity of the task on honing in on the earliest age where cognitive decline can be detected. Although the water maze is a valid and reliable task for measuring spatial learning, limitations include a problematic test–retest effect making pharmacological, interventional, or longitudinal studies difficult to conduct. However, an odor discrimination task has recently been developed that is appropriate for a wide variety of experiments requiring a retest situation. An explanation of this task will include discussion of other experimental designs involving odor cues used in aging studies and the validity in various rat strains.