E2 and ER-specific agonists regulate mobility and anxiety-like behaviours in OVX rats. (A) Experimental regimen. Female Sprague–Dawley rats were ovariectomized at day 0 (9 mo of age), when irregular estrous cycles usually begin in laboratory rodents. They were then separated into 2 treatment groups: early and late ET, with different durations of ovarian hormone deprivation (6 d and 180 d). This experimental paradigm mimicked a common clinical setting, in which perimenopausal women (about 50 yr of age) receive ET at different points postmenopause. In the early ET group, OVX rats were treated with either E2 or vehicle (corn oil) at day 7 (equal to 4 mo in humans). In the late ET group, OVX rats were treated with E2, DPN, PPT or vehicle at day 181 (equal to age > 11 yr in humans). After 2 days of treatment, rats were subjected to a forced swim test, and samples were collected on the following day. (B) Behavioural tests. The forced swim test (a, c) as an assessment of antidepressant activity and the elevated plus maze (b, d) as an assessment of anxiety-like behaviour were performed in rats treated with vehicle or E2 6 days post-OVX (a, b) or vehicle, E2, DPN or PPT 180 days post-OVX (c, d). Data were analyzed using 1-way ANOVA and a subsequent Bonferroni post hoc test, and are presented as mean ± SEM, n = 6 for early ET, n = 5 for late ET. #p < 0.05 v. sham + V; *p < 0.05 v. OVX + V. ANOVA = analysis of variance; DPN = diarylpropionitrile; E2 = estradiol; ER = estrogen receptor; ET = estrogen therapy; FST = forced swim test; OVX = ovariectomy; PPT = propylpyrazoletriol; Sac = sacrifice; SEM = standard error of the mean; V = vehicle.