Aging and corticosterone injections affect spatial learning in Fischer-344 X Brown norway rats.

The hippocampus is one of the first brain structures to show age-related changes. Moreover, hippocampal neurons are endangered by prolonged exposure to high circulating levels of corticosterone with stress or aging. We examined the effects of aging and high corticosterone levels on spatial learning, a key hippocampal function. Young (4-6 months), old (23-25 months), and very old (31 months) male Fischer-344xBrown Norway (F-344xBN) rats received six pre-testing days in the Morris water task to determine baseline spatial learning performance. Next, half the animals in each group were given daily corticosterone injections for 15 days. During the last six injection days, all animals underwent post-testing in the Morris water task with the environment and goal location changed. Baseline, peak, and clearance plasma corticosterone levels were determined. During pre-testing, old animals swam as directly to the goal as the young, but very old animals were significantly impaired. During post-testing, both old and very old non-injected animals had significantly greater directional heading errors and flatter learning curves than the young. Among injected animals, the very old performed as well as the young, but the old did not. Old animals who did not show improvement during the first three pre-testing days were responsible for the old impairment during post-testing. Thus, only very old F-344xBN rats are impaired when initially exposed to a spatial learning task, but half the old and all very old animals are impaired when the environment is changed. Very old F-344xBN rats, however, demonstrate enhanced spatial learning when exposed to corticosterone injections.