Long-term replacement of estrogen in combination with medroxyprogesterone acetate improves acquisition of an alternation task in middle-aged female rats

Abstract

Studies have shown that ovarian hormones protect against some of the cognitive deficits associated with aging. Although much of the literature in rodents has focused on hippocampal dependent tasks, studies suggest that tasks dependent on the prefrontal cortex are also influenced by ovarian hormones. The present study investigated the effects of ovarian hormone treatment during aging on a delayed alternation t-maze. Female Long Evans hooded rats were ovariectomized at middle age (11-12 months) and placed in 1 of 5 treatment groups: no replacement, chronic estradiol (E(2)), cyclic E(2), chronic E(2) and progesterone, or chronic E(2) and medroxyprogesterone acetate (MPA). Following 6 months of hormone treatment, animals were trained to alternate in a t-maze. After reaching criterion, a series of delays from 5 to 90 s were introduced in random order. Rats receiving E(2) with MPA reached criterion significantly faster than animals not receiving treatment and those who received chronic or cyclic E(2) only. There was a nonsignificant trend for animals receiving E(2) and progesterone to reach criterion in fewer sessions than animals receiving E(2) only. Mode of administration, cyclic or chronic, did not affect performance. Hormones did not affect performance on the delayed alternation. This study, in combination with previous research, indicates that hormone effects cannot be generalized across tasks, age, or duration, and long-term estrogen in combination with MPA can be beneficial for some tasks.

Figure 1

Mean ± SEM number of sessions to criterion for no delay alternation trials. Animals receiving E₂ + MPA required fewer sessions to reach criterion than animals in three groups: no replacement (p < .04), chronic E₂ (p < .02), and cyclic E₂ (p < .02). There were non-significant trends for animals that received E₂ + P to require fewer days to meet criterion than animals receiving chronic E₂ (p < .09) and cyclic E₂ (p < .08). * = p<.05

Figure 2

Mean number correct at each alternation delay. There was a significant effect of Delay (p <.01) such that increasing the intertrial delay significantly reduced performance in all treatment groups. Hormone treatment was not significant.