A pubertal immune challenge alters the antidepressant-like effects of chronic estradiol treatment in inbred and outbred adult female mice

Abstract

Puberty is a period characterized by brain reorganization that contributes to the development of neural and behavioral responses to gonadal steroids. A single injection of the bacterial endotoxin, lipopolysaccharide (LPS), during the pubertal period decreases sexual receptivity in response to ovarian hormones in adulthood. Because chronic estradiol treatment alleviates depression-like symptoms in ovariectomized adult mice, we investigated the effect of pubertal LPS treatment on estradiol's antidepressant effects. We hypothesized that pubertal LPS treatment would decrease the antidepressant-like effect of estradiol in adult ovariectomized female mice, as it decreases other behavioral responses to ovarian hormones. As expected, chronic estradiol treatment decreased depression-like behavior, as measured by the duration of immobility, in saline-treated mice from two different strains, as well as in mice treated with LPS in adulthood. In contrast, in mice treated pubertally with LPS, estradiol strikingly increased the duration of immobility. No difference in body weight and in locomotion was found among the groups, suggesting that the differences in depression-like behavior were not due to differences in body weight or locomotor activity between LPS-treated and control mice. These results suggest that exposure to an immune challenge during the pubertal period alters the responsiveness of depression-like behavior to estradiol.

Keywords: ANOVA; ER; LPS; analyses of variance; depression; estrogen receptors; forced swim test; lipopolysaccharide; puberty; stress; tail suspension test.

Figure 1

Graphical schematic of the experimental design for Experiment 1.

Figure 2

Graphical schematic of the experimental design for Experiment 2.

Figure 3

A) Sickness score (Mean ± SEM) and B) percent body weight (Mean ± SEM) change in C57Bl/6 mice treated with either saline or LPS at 6 or 8 weeks old. Significantly greater than saline controls: *p < 0.05.

Figure 4

Duration of immobility (Mean ± SEM) during A) the forced swim test and B) the tail suspension test in C57Bl/6 mice treated with saline or LPS at six or eight weeks old and treated either with estradiol or oil vehicle in adulthood. Significant difference between mice treated with estradiol and those treated with oil-vehicle: ^*p < 0.05.

Figure 5

A) Sickness score (Mean ± SEM) and B) percent body weight (Mean ± SEM) change in CD1 mice treated with either saline or LPS at six or ten weeks old. Significantly greater than saline controls: ^*p < 0.05.

Figure 6

Duration of immobility (Mean ± SEM) during A) the forced swim test and B) the tail suspension test in CD1 mice treated with saline or LPS at six or ten weeks old and treated either with estradiol or oil vehicle in adulthood. Significant difference between mice treated with estradiol and those treated with oil-vehicle: ^*p < 0.05.