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

Experimental procedure.

In Experiment 1, mice received a single s.c. injection of either oil vehicle (control, 0.1 ml sesame oil) or various doses (0.5 μg/0.1 ml, 5 μg/0.1 ml, or 50 μg/0.1 ml) of EB 7 days post-ovariectomy. Fear conditioning was conducted 2 days after EB treatment, and the mice were tested for their conditioned fear responses the following day. In Experiment 2, mice were ovariectomized and implanted s.c. with a Silastic capsule (I.D. 1.98 × 20.0 mm) containing either vehicle or various doses (0.05 μg, 0.5 μg, 5 μg, 50 μg/0.1 ml) of EB. Two weeks post-implantation, fear conditioning and testing were conducted. In the conditioning phase, 3 min after being placed in the chamber, mice were administered three consecutive foot shocks (duration: 2 s, 0.8 mA) with 30 s intershock intervals. The day after the last behavioral test, the animals were sacrificed using a pentobarbital overdose. The uteri were collected and the wet weights were recorded. In Experiment 3, mice were ovariectomized and implanted (s.c.) with a Silastic capsule (I.D. 1.98 × 20.0 mm) containing either vehicle or various doses (0.05 μg, 0.5 μg, 5 μg, 50 μg/0.1 ml) of EB. Two weeks post-implantation, the animals were decapitated and their trunk blood was collected for the hormonal assay.</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

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

Uterine weight.

<p>Uterine weight.</p

Improving Charge/Discharge Properties of Radical Polymer Electrodes Influenced Strongly by Current Collector/Carbon Fiber Interface

Charge/discharge processes of organic radical batteries based on the radical polymer’s redox reaction are largely influenced by carbon fibers consisting in the composite electrodes to help electron transfer. To find the optimal structure of the composite electrodes, the dominant electron transfer processes were determined by ac impedance measurement of the composite electrodes. A strong correlation between the overall electron transfer resistance of the composite electrodes and the materials of the current collector suggests that the electric conduction to the current collector through the contact resistance should be crucial. It was also confirmed that the charge/discharge performance of the composite electrode was related to the overall electron transfer resistance of the composite electrode. These results indicated that the charge/discharge performance of the radical battery was dominated by the interfacial electron transfer processes at the current collector/carbon fiber interface and that the rate performance would be much improved by suitably designing the interfacial structure