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Estrogen Receptor-Selective Agonists Modulate Learning in Female Rats in a Dose- and Task-Specific Manner
Samantha L Pisani1, Steven L Neese1, John A Katzenellenbogen1
1Neuroscience Program (S.L.P., S.L.N., S.L.S., D.L.K.) and Department of Chemistry (J.A.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (S.L.N., S.L.S.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Department of Psychology and Neuroscience (S.L.N.), Baldwin Wallace University, Berea, Ohio 44017; and Department of Biology (D.L.K.), Syracuse University, Syracuse, New York 13244.
Estrogen receptor subtypes differentially affect learning. Selective compounds targeting estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) enhanced spatial learning while impairing response learning in female rats.
Area of Science:
- Neuroscience
- Endocrinology
- Behavioral Pharmacology
Background:
- Estrogens influence hippocampus-dependent cognition positively but can impair striatum-dependent learning.
- The specific estrogen receptor (ER) subtypes mediating these opposing effects on learning remain largely unknown.
- Understanding ER subtype roles is crucial for predicting cognitive effects of ER-targeting therapies.
Purpose of the Study:
- To investigate the distinct roles of ERα and ERβ in modulating place and response learning.
- To examine the effects of ERα-selective and ERβ-selective compounds on different types of learning.
Main Methods:
- Ovariectomized female rats were treated with ERα-selective (propyl pyrazole triol) or ERβ-selective (diarylpropionitrile, Br-ERb-041) compounds.
- A dose-response study was conducted using subcutaneous injections 48 and 24 hours before behavioral testing.
- Rats were trained on place learning (hippocampus-sensitive) and response learning (striatum-sensitive) tasks.
Main Results:
- All tested compounds (propyl pyrazole triol, diarylpropionitrile, Br-ERb-041) enhanced place learning.
- All compounds impaired response learning, with distinct dose-response patterns observed for each compound and task.
- ERα and ERβ were detected in both the hippocampus and striatum.
Conclusions:
- Both ERα and ERβ activation modulate learning processes.
- Activation of either ER subtype can enhance place learning and impair response learning.
- These findings highlight the complex, subtype-specific actions of estrogens on cognition.
