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. 2010 Jul;58(2):200-7.
doi: 10.1016/j.yhbeh.2010.03.018. Epub 2010 Apr 1.

Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats

Nioka C Lowry  1 , Laura P Pardon, Melissa A Yates, Janice M Juraska
Affiliations

Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats

Nioka C Lowry et al. Horm Behav. 2010 Jul.

Abstract

Although previous research has indicated that hormone replacement therapy benefits memory in menopausal women, several recent studies have shown either detrimental or no effects of treatment. These inconsistencies emphasize the need to evaluate the role of ovarian hormones in protecting against age-related cognitive decline in an animal model. The present study investigated the effects of long-term hormone treatment during aging on the Morris water maze. Female Long Evans hooded rats were ovariectomized at middle age (12-13 months) and were immediately placed in one of five groups: no replacement, chronic 17 beta-estradiol only, chronic 17 beta-estradiol and progesterone, chronic 17 beta-estradiol and medroxyprogesterone acetate (MPA), or cyclic 17 beta-estradiol only. 17 beta-estradiol was administered in the drinking water in either a chronic or cyclic (3 out of 4 days) fashion. Progesterone and MPA were administered via subcutaneous pellets. Following 6 months of hormone treatment, animals were tested on the Morris water maze. Animals performed four trials a day for 4 days and after the final day of testing a subset of animals completed a probe trial. Across 4 days of testing, rats receiving 17 beta-estradiol in combination with MPA performed significantly worse than all other groups receiving hormone replacement. In addition on the last day of testing, chronic 17 beta-estradiol administration was more beneficial than cyclic administration and no replacement. Thus compared to other hormone-treated groups, long-term 17 beta-estradiol treatment in combination with MPA results in impaired performance on the spatial Morris water maze.

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Figures

Figure 1
Figure 1
Mean latency to find the visible platform during four trials of pretraining. There were no significant differences between groups.
Figure 2
Figure 2
Mean ± SEM latency (A) and pathlength (B) to find the submerged platform averaged across four days of testing for all groups. The E + MPA group had significantly longer latencies (E: p < .01; E + P: p < .03; CYE: p < .03) and pathlengths (E: p < .01; E + P: p < .04; CYE: p < .01) than all other groups receiving hormone replacement.
Figure 3
Figure 3
Mean ± SEM latency (A) and pathlength (B) to find the submerged platform for eight blocks (each consisting of two trials) of testing for all groups. Preplanned comparison of Block 2 versus 3, 4 versus 5, and 6 versus 7 found that none of the groups forgot the task over night except for E + MPA between Block 6 and 7 (p < .04).
Figure 4
Figure 4
Mean ± SEM latency (A) and pathlength (B) to find the submerged platform for each of the four days of testing for all groups. The group receiving chronic 17 β-estradiol performed better on Day 4 than both NR and CYE groups. * (p < .05); # indicates a trend (p < .09).
Figure 5
Figure 5
Mean ± SEM time spent in the target quadrant during the first thirty seconds of the probe trial for all groups. There were no significant differences between groups.
See this image and copyright information in PMC

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