The timing and duration of estradiol on social behavior and gene expression in mature adult and aging female rats

Abstract

Menopause causes declines in ovarian hormones such as estrogens and progesterone. During the menopausal transition, women may experience adverse symptoms such as anxiety, depression and lack of desire to interact. However, since the publication of the Women’s Health Initiative (WHI) many women have been left asking questions about whether, when, and how long to take hormone treatments for menopausal symptoms. This dissertation focuses on the effects of timing and duration of estradiol (E2) relative to loss of ovarian hormones (OVX) on the social brain and behavior in mature adult (MAT) and aging (AG) female rats. The results from these studies illustrated that in MAT rats, 3-months of E2 given immediately following OVX decreased communications and social interactions between cagemates, as assessed in a test quantifying the number of ultrasonic vocalizations emitted, as well as time spent interacting with one another. I interpret this result to mean that the E2 animals had improved social memory. In MAT rats gene expression of the neuropeptides (Oxt, Avp, Oxtr, Avpr1a) involved in regulating social behavior were also greater in the BNST, MeA, and SON of rats treated with estradiol compared to vehicle. Because menopause typically happens at middle age, I conducted a similar experiment in middle-aged rats to assess the influence of estradiol deprivation or replacement in aging rats. Aging animals were behaviorally characterized twice (at 3 and 6-months), groups were given different timing and duration of estradiol or vehicle treatments as a model for the WHI. Similar to the MAT animals, the estradiol-treated AG rats called less than their vehicle counterparts during an ultrasonic vocalization test conducted at the 3-month testing period. However, at the 6-month testing period no differences were observed, which could be the result of aging. Oxt, Oxtr, Avp and Avpr1a showed unique gene expression patterns that were dependent upon the timing and duration of estradiol in a region-specific manner in the AG rats. Most genes were up-regulated by estradiol treatment, irrespective of timing or duration. Overall this work may benefit the field of women’s health through new knowledge on consequences of age, and the timing and duration of estrogen treatment, on the social brain and behavior.