Enduring influences of peripubertal/adolescent stressors on behavioral response to estradiol and progesterone in adult female mice

Abstract

Exposure to stressors during particular stages of development leads to acute and long-term physiological and behavioral changes. We have reported that shipping mice during the peripubertal/adolescent period results in decreased induction of feminine sexual behavior by estradiol and progesterone in adult female mice. To study further the factors involved in this decreased behavioral response, female mice were exposed to a variety of experimental stressors when 6 wk old. Effects of peripubertal/adolescent exposure to these stressors on acute plasma corticosterone levels and changes in body weight and adult behavioral response to estradiol and progesterone were assessed. Although restraint for three daily 3-h periods, 36-h food deprivation, or a multiple stressor regimen acutely increased plasma corticosterone levels and reduced body weight, only exposure to particular doses of the bacterial endotoxin lipopolysaccharide (LPS; 1-1.5 mg/kg body weight, doses that induced moderate levels of sickness behavior in these studies) resulted in reduced behavioral response to estradiol and progesterone in adulthood. Like the effects of shipping, the effects of LPS on adult feminine sexual behavior appear most robust when injected at 6 wk old and are limited to exposure during a vulnerable period at approximately 4-6 wk of age. Therefore, an immune stressor during the peripubertal/adolescent period, but not restraint, food restriction, or a combined stressor, has an enduring influence on behavioral response to estradiol and progesterone. This demonstrates that the decreased response to estradiol and progesterone is not a general response to all stressors during this developmental stage.

Figure 1

A, LQ (mean ± sem); B, plasma corticosterone levels; C, percent body weight change of female mice exposed to 3 h restraint at 6 wk old. As a point of reference, the body weight loss at d 3, t = 3 h, corresponds to a 0.87-g loss in body weight contrasted with d 3, t = 0 h. The lower x-axis refers to the animal’s age at time of testing, blood sample, or body weight. Significant differences between restraint and control groups at specific time points are indicated: ***, P < 0.001.

Figure 2

A, LQ (mean ± sem); B, plasma corticosterone levels; C, percent body weight change of female mice exposed to food deprivation at 6 wk old. The lower x-axis refers to the animal’s age at time of testing, blood sample, or body weight. Significant differences between restraint and control groups at specific time points are indicated: ***, P < 0.001.

Figure 3

A, LQ (mean ± sem); B, plasma corticosterone levels [t = 0 (pretreatment on particular day), t = 1 (after first stressor exposure on particular day), t = 3 (after third stressor exposure on particular day)]; C, percent body weight change of female mice exposed to multiple stressor conditions at 6 wk old. The lower x-axis refers to the animal’s age at time of testing (A) or body weight (C). Significant differences between restraint and control groups at specific time points are indicated: ***, P < 0.001.

Figure 4

A, LQ (mean ± sem); B, plasma corticosterone levels; C, percent body weight change of female mice injected with various doses of LPS at 6 wk old; D, LQ (mean ± sem) of female mice exposed to one 1.5 mg/kg dose of LPS at 6 wk old. The lower x-axis refers to the animal’s age at time of testing, blood sample, or body weight. In A, significant differences between restraint and control groups at specific time points are indicated: a, P < 0.05; b, P < 0.01; c, P < 0.001. In B–D: *, P < 0.05; **, P < 0.01; ***, P < 0.001; and a, no significant difference among these groups (B).

Figure 5

LQ (mean ± sem) of female mice injected with 1.5 mg/kg LPS at 3, 4, 5, 6, 7, 8, or 10 wk of age. The lower x-axis refers to the animal’s age at time of testing. Significant differences between restraint and control groups at specific time points are indicated: *, P < 0.05.