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This version published online on October 28, 2004
Endocrinology, doi:10.1210/en.2004-1158
A more recent version of this article appeared on February 1, 2005
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*Anxiety

Submitted on August 31, 2004
Accepted on October 19, 2004

Novel Actions of Estrogen Receptor Beta on Anxiety-Related Behaviors

Trent D. Lund*, Tomislav Rovis, Wilson C. J. Chung, and Robert J. Handa

Department of Biomedical Sciences and Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523

* To whom correspondence should be addressed. E-mail: tlund{at}colostate.edu.

Estrogens are reported to have both anxiogenic and anxiolytic properties. This dichotomous neurobiological response to estrogens may be mediated by the existence of two distinct estrogen receptor (ER) systems, ER{alpha} and ER{beta}. In brain, ER{alpha} plays a critical role in regulating reproductive neuroendocrine function, whereas ER{beta} may be more important in regulating non-reproductive functions. To determine if estrogens' anxiolytic actions could be mediated by ER{beta}, we examined anxiety-related behaviors following treatment with ER subtype selective agonists. Ovariectomized female rats, divided into 4 treatment groups, were injected with the selective ER{beta} agonist diarylpropionitrile (DPN), the ER{alpha} selective agonist propyl-pyrazole-triol (PPT), 17{beta}-estradiol or vehicle daily for 4days. Following injections, behavior was monitored in the elevated plus-maze (EPM) or open field (OF). Rats treated with DPN showed significantly decreased anxiety-related behaviors in both behavioral paradigms. In the EPM, DPN significantly increased the number of open arm entries and time spent on the open arms of the maze. Furthermore, DPN significantly reduced, while PPT increased, anxiogenic behaviors such as the number of fecal boli and time spent grooming. In the OF, DPN treated females made more rears, interacted more with a novel object and spent more time in the middle of the OF than did control or PPT-treated rats. To confirm that DPN's anxiolytic actions are ER mediated, the non-selective ER antagonist, tamoxifen, was administered alone or in combination with DPN. Tamoxifen blocked the previously identified anxiolytic actions of DPN. Taken together these findings suggest that the anxiolytic properties of estrogens are ER{beta}-mediated.




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