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*Anxiety
Endocrinology Vol. 146, No. 2 797-807
Copyright © 2005 by The Endocrine Society

Novel Actions of Estrogen Receptor-ß on Anxiety-Related Behaviors

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

Departments of Biomedical Sciences (T.D.L., W.C.J.C., R.J.H.) and Chemistry (T.R.), Colorado State University, Fort Collins, Colorado 80523

Address all correspondence and requests for reprints to: Trent D. Lund, Ph.D., Department of Biomedical Science, Colorado State University, Anatomy W103, 1617 Campus Delivery, Fort Collins, Colorado 80523-1670. 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 ERß. In brain, ER{alpha} plays a critical role in regulating reproductive neuroendocrine function, whereas ERß may be more important in regulating nonreproductive functions. To determine whether estrogen’s anxiolytic actions could be mediated by ERß, we examined anxiety-related behaviors after treatment with ER subtype-selective agonists. Ovariectomized female rats, divided into four treatment groups, were injected with the selective ERß agonist diarylpropionitrile (DPN), the ER{alpha}-selective agonist propyl-pyrazole-triol (PPT), 17ß-estradiol, or vehicle daily for 4d. After injections, behavior was monitored in the elevated plus maze or open field. Rats treated with DPN showed significantly decreased anxiety-related behaviors in both behavioral paradigms. In the elevated plus maze, DPN significantly increased the number of open arm entries and time spent on the open arms of the maze. Furthermore, DPN significantly reduced, whereas PPT increased, anxiogenic behaviors such as the number of fecal boli and time spent grooming. In the open field, DPN-treated females made more rears, interacted more with a novel object, and spent more time in the middle of the open field than did control or PPT-treated rats. To confirm that DPN's anxiolytic actions are ER mediated, the nonselective 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 ERß mediated.




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