Long-term alteration of anxiolytic effects of ovarian hormones in female mice by a peripubertal immune challenge

Abstract

Recent reports indicate that exposure to some stressors, such as shipping or immune challenge with the bacterial endotoxin, lipopolysaccharide (LPS), during the peripubertal period reduces sexual receptivity in response to ovarian hormones in adulthood. We hypothesized that a peripubertal immune challenge would also disrupt the response of a non-reproductive behavior, anxiety-like behavior, to ovarian hormones in adulthood. Female C57Bl/6 mice were injected with LPS during the peripubertal period and tested for anxiety-like behavior in adulthood, following ovariectomy and ovarian hormone treatment. Treatment with estradiol followed by progesterone reduced anxiety-like behavior in control, but not LPS-treated females. We next determined if the disruptive effect of LPS on adult behavior were limited to the peripubertal period by treating mice with LPS either during this period or in adulthood. LPS treatment during the peripubertal period disrupted the anxiolytic effect of ovarian hormones, whereas treatment in adulthood did not. We further tested if this model of peripubertal immune challenge was applicable to an outbred strain of mice (CD-1). Similar to C57Bl/6 mice, LPS treatment during the peripubertal period, but not later, disrupted the anxiolytic effect of estradiol and progesterone. These data suggest that a peripubertal immune challenge disrupts the regulation of anxiety-like behavior by ovarian hormones in a manner that persists at least for weeks after the termination of the immune challenge.

Puberty and adolescence as a time of vulnerability to stressors that alter neurobehavioral processes

“…Female C57Bl/6 mice injected with LPS at four, five or six weeks, but not three, seven, eight, or ten weeks old expressed a decrease in sexual receptivity in adulthood, compared to saline-injected controls (Laroche et al, 2009a), duplicating the same developmental sensitive period demonstrated by mice shipped at these same ages (Laroche et al, 2009b). Subsequent work has demonstrated that pubertal and adult animals display similar increases sickness behavior (e.g., lethargy, huddling, piloerection, and ptosis) and decreases in body weight following LPS administration (Ismail and Blaustein, 2013; Ismail et al, 2011; Ismail et al, 2012; Olesen et al, 2011). …”

Enduring influence of pubertal stressors on behavioral response to hormones in female mice

“…In studies of anxiety-like behavior, an injection of estradiol benzoate (EB, 2 µg sc ) followed 44 hours later by an injection of progesterone (100 µg sc ), similar to the treatment used in tests of female sexual behavior, causes a decrease in anxiety-like behavior, assessed by the elevated plus maze, light-dark box and marble burying test (Olesen et al, 2011). Pubertal immune challenge had very similar effects in both C57Bl/6 and CD1 strains of mice.…”

“…In general, the hormone treatments were anxiolytic in mice that were injected with saline at 6 or 8 weeks old and in mice injected with LPS at 8 weeks old. However, in mice given the immune challenge at 6 weeks old during the pubertal period, hormone treatment had either an anxiogenic effect or no effect (Olesen et al , 2011), suggesting that pubertal immune challenge caused a major change in response to estradiol and progesterone. It should be noted that there was a tendency for LPS to reduce anxiety-like behavior in both the light-dark box and the elevated plus maze.…”

“…The latency to cover three marbles at ¾ or more with bedding was assessed to examine anxiety-like behavior. Reprinted from (Olesen et al , 2011) with permission of Elsevier, Copyright 2011 .…”

Prenatal Exposure to Lamotrigine: Effects on Postnatal Development and Behaviour in Rat Offspring

“…Progesterone and estrogen induce anxiolytic behaviour in C57BL/6 female mice [32]. Further, estrogen suppresses GABA-A receptor expression thereby slowing down the GABA mediated inhibition [33].…”