Involvement of nuclear progesterone receptors in the formation of anxiety in female mice.

We report here studies on the delayed effects of exogenous progesterone on the formation of anxiety in female mice. Ovariectomized female mice were given seven days of replacement therapy either with the two main ovarian hormones-progesterone and estradiol benzoate-or with progesterone only; levels of anxiety were measured six hours later in the elevated plus-maze. The role of nuclear progesterone receptors in controlling the level of anxiety was assessed by giving some mice injections of the synthetic progesterone receptor blocker mifepristone 2 h before the last dose of hormones. An immunohistochemical method was used to study changes in the number of nuclear progesterone receptors in different areas of the brains of experimental animals. These studies showed that progesterone has a delayed enhancing effect on anxiety in female mice. The role of nuclear progesterone receptors in forming this behavioral characteristic was supported by a strong correlation between changes in the numbers of progesterone receptor-immunopositive cells in several brain structures and the level of anxiety. Prior blockade of progesterone receptors using mifepristone led to a maximal reduction in the level of anxiety, which was also evidence for a role for the genomic mechanisms of action of progesterone in controlling anxiety in females.