Effect of freezing and locomotion durations on contextual fear conditioning in Experiment 2.

<p>OVX mice were implanted s.c. with a Silastic capsule containing either vehicle (EB0L), 0.05 μg/0.1 ml (EB0.05L), 0.5 μg/0.1 ml (EB0.5L), 5 μg/0.1 ml (EB5L), or 50 μg/0.1 ml (EB50L) 14 days before conditioning. Mean (± SEM) duration of freezing (A) and locomotion (B) in the 10 min test conducted 24 h after conditioning. Mice treated with EB50L showed a significantly longer freezing time compared with control (<i>p</i> < 0.05) and EB5L (<i>p</i> < 0.05) mice. EB50L mice also displayed a significantly shorter locomotion time compared to control mice (<i>p</i> < 0.05). Significant differences are denoted by an asterisk; *<i>p</i> < 0.05.</p

The enhancement effect of estradiol on contextual fear conditioning in female mice

<div><p>Several studies have reported regulatory effects of estrogens on fear conditioning in female rodents. However, these studies used different doses, durations, and/or administration methods, and reported inconsistent results. To clarify the effect of estrogen on fear conditioning, we investigated the effects of different doses and durations of estradiol administration on freezing behavior during contextual fear conditioning in ovariectomized (OVX) mice. In Experiment 1, OVX ICR mice received a single subcutaneous (s.c.) injection of either oil vehicle (control, 0.1 ml sesame oil) or varied doses (0.5 μg/0.1 ml, 5 μg/0.1 ml, or 50 μg/0.1 ml) of 17β-estradiol-3-benzoate (EB). Fear conditioning was conducted two days post-EB treatment, and the mice were tested for the learned fear response the following day. In Experiment 2, OVX female mice received an s.c. implantation of a Silastic capsule (I.D. 1.98 × 20.0 mm) containing either vehicle or varied doses (0.05 μg/0.1 ml, 0.5 μg/0.1 ml, 5 μg/0.1 ml, 50 μg/0.1 ml) of EB. Two weeks after implantation, fear conditioning was conducted. During the tests conducted 24 h after conditioning, the high dose EB group showed longer freezing times in both experiments, and lower locomotor activity compared to the control or lower dose groups. In Experiment 3, serum estradiol concentrations of the mice that were treated like those in Experiment 2, were measured; the serum levels of estradiol increased linearly according to the dose of EB administered. The results suggest that mice treated with a high dose of EB exhibit enhanced fear learning, regardless of treatment duration. As a woman’s vulnerability to emotional disorders increases in the peripregnancy period, during which estrogen levels are high, the results from the high-dose EB groups may be important for understanding the hormonal mechanisms involved in these disorders.</p></div

Uterine weight.

<p>Uterine weight.</p

Effect of freezing and locomotion durations on contextual fear conditioning in Experiment 1.

<p>OVX mice received a single s.c. injection of EB at a dose of 0.5 μg/0.1 ml (EB0.5S), 5 μg/0.1 ml (EB5S), or 50 μg/0.1 ml (EB50S), or an oil vehicle (EB0S) two days before conditioning. The mean (± SEM) duration of freezing (A) and locomotion (B) in the 10-min test conducted 24 h after conditioning is shown. Mice treated with a high dose of EB (EB50S) displayed significantly more freezing than control and EB5S mice (<i>p</i> < 0.05). Significant differences are denoted by an asterisk; *<i>p</i> < 0.05.</p