No detectable changes in anxiety-related and locomotor behaviors in adult ovariectomized female rats exposed to estradiol, the ERβ agonist DPN or the ERα agonist PPT

The sex steroid hormone 17 beta-estradiol (estradiol) and its Estrogen Receptors (ERs) have been linked to modu-lation of anxiety-related and locomotor behaviors in female rodents. Research suggests that estradiol mitigates anxiety-related behaviors through activating Estrogen Receptor (ER)beta and increases locomotor behaviors through ER alpha. The influence of ERs on these behaviors cannot always be detected. Here we discuss two experi-ments in which we tested the hypothesis that anxiety-related behaviors would decrease after ER beta activation and locomotor behaviors would increase after ER alpha activation, and also assessed the persistence of these behavioral effects by varying the timing of behavioral testing. Two cohorts of adult female ovariectomized rats were exposed to estradiol, the ER beta agonist DPN, the ER alpha agonist PPT, or oil for four consecutive days. Body mass was assessed throughout as a positive control. In both cohorts, open field behaviors were assessed on the first day of exposure. In one cohort (Experiment 1), open field, light/dark box, and elevated plus maze behaviors were assessed on the final day of injections. In the second cohort (Experiment 2), these behaviors were assessed 24 h after the final exposure. As expected, significant differences in body mass were detected in response to estradiol and PPT exposure, validating the estradiol and ER manipulation. No significant differences were observed in anxiety -related or locomotor behaviors across treatment groups, indicating that the efficacy of these agonists as thera-peutic agents may be limited. We review these results in the context of previous literature, emphasizing relevant variables that may obscure ER-related actions on behavior.