Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas

Abstract

Acute effects of estrogens on mnemonic processes were examined at the behavioral and neurochemical levels. 17beta-estradiol and 17alpha-estradiol influences on memory consolidation were assessed using object placement (OP) and object recognition (OR) tasks. Subjects received treatment immediately after a sample trial (exploring two novel objects), and memory of objects (OR memory) or location of objects (OP memory) was tested 4h later. Both isomers of estradiol enhanced memory. For spatial memory, 15 and 20 microg/kg of 17beta-estradiol facilitated OP, while lower and higher doses were ineffective. 17alpha-estradiol had a similar pattern, but a lower dose was effective. When treatment was delayed until 45 min after a sample trial, memory was not enhanced. For non-spatial memory, OR was facilitated at 5 microg/kg of 17beta-estradiol and at 1 and 2 microg/kg of 17alpha-estradiol and, similar to OP, lower and higher doses were ineffective. These data demonstrate that beneficial effects of estrogens are dose, time and task dependent, and the dose-response pattern is an inverted U. Because monoamines are known to have contributions to memory, brains were removed 30 min after treatment for measurements of dopamine (DA), norepinephrine (NE), serotonin (5-HT), and metabolites. Estrogen elevated 5HT, NE metabolite MHPG, turnover ratio of NE to MHPG, and DA metabolite DOPAC levels in the prefrontal cortex, while NE and MHPG were decreased in the hippocampus. Thus, acute estrogens exert rapid effects on memory consolidation and neural function, which suggests that its mnemonic effects may involve activation of membrane associated estrogen receptors and subsequent signaling cascades, and that monoamines may contribute to this process.

Copyright 2010 Elsevier Inc. All rights reserved.

Figures

FIG. 1

Timeline for hormone treatment. A. OVX rats received a single sc injection of either vehicle or estradiol immediately after T1 (immediate post-T1 treatment) or 45min after T1 (delayed post-T1 treatment). B. For neurochemical analysis, treatment was given immediately after T1. Subjects were sacrificed 30 min after treatment.

FIG. 2

Acute effects of 17β-E2 on object placement (OP). Exploration ratios during retention trials are shown and the dashed line at 0.5 indicates chance level performance (rats spent equal amount of time around objects at old and new locations). n=9-10 in each group. A. OIL vs.60μg/kg of E2. Not significant. B. OIL vs.40μg/kg of E2. Not significant. C. OIL vs.30μg/kg of E2. Significant interaction (F 1, 16=7.97, p<0.012), but no group difference in exploration ratios (t 16=1.978, p<0.065). D. OIL vs.20μg/kg of E2. Significant interaction (F1,18=10.67, p<0.004) and group differences in exploration ratios (t 18=2.943, p<0.009) were found. E. OIL vs.15μg/kg of E2. Significant interaction (F1, 17=8.51, p<0.01) and exploration ratios (t 17=2.988, p<0.008) were found. F. OIL vs. 10μg/kg of E2. Not significant. Data were analyzed by two-way ANOVA (group × location) with two sample t tests. Entries are means ± SEM. *p<0.05; **p<0.01.

FIG. 3

Dose-response for 17β-E2 and memory performance. Data were analyzed by one-way ANOVA with post-hoc test (Fisher LSD). The dashed line at the exploration ratio of 0.5 indicates chance level performance (rats spent equal amount of time around objects at old and new locations). A. Object Placement (OP). ANOVA was significant, F 4, 47=3.191, p<0.021, and 20μg/kg E2 enhanced OP memory (p<0.002). B. Object Recognition (OR). ANOVA was significant, F 3, 52=3.604, p<0.019 and 5μg/kg enhanced memory (p<0.02). Entries are means ± SEMs. *p<0.05; ** p <0.01.

FIG. 4

Immediate (A) vs. delayed postT1 treatment (B) with 20μg/kg of 17β-E2 on OP. Left panels: exploration times around objects during T1. Middle panel: time spent exploring objects at old and new locations during T2. Right panel: exploration ratios during T2. Dashed lines at 0.5 indicate chance level performance. Entries are means ± SEM. **p

FIG. 5

Acute effects of 17β-E2 on object recognition (OR). Time spent around objects during T1 (Left), T2 (Middle) and exploration ratios during T2 (Right). T2 Data were analyzed by two-way ANOVA (group × object) with post-hoc tests. n=9-10. T1 exploration time was not significant for all groups. A. OIL vs. 5ug/kg of E2. Significant interaction (F 1, 16= 10.49, p<0.005) was found and exploration ratios (p<0.04) were different from the control. B. OIL vs. 10ug/kg of E2. Significant interaction (F 1, 17=9.038, p<0.008) was found. C. OIL vs. 15ug/kg of E2. Not significant by ANOVA. Entries are means ± SEM. * P < 0.05, ** p<0.01

FIG.6

Dose-response for 17α-E2 and memory performance. Data were analyzed by one-way ANOVA with post-hoc test (Fisher LSD). The dashed line at the exploration ratio of 0.5 indicates chance level performance (rats spent equal amount of time around objects at old and new locations). A. Object Placement (OP). ANOVA was significant, F 3, 30=4.06, p<0.015, and 5μg/kg of E2 enhanced OP memory (p<0.0019). B. Object Recognition (OR). ANOVA was significant, F 4, 38=2.763, p<0.041 and both 1μg/kg (p<0.013) and 2ug/kg (p<0.02) of E2 enhanced memory. Entries are means ± SEMs. *p<0.05.