Gore, A. C. | bioRxiv Science

bioRxiv2021

Hormonal contraceptives alter amphetamine place preference and responsivity in the intact female rat.

Hormonal contraceptives (HCs) are commonly used among reproductive aged women and alter the physiological state of the user by interfering with endogenous hormone concentrations and their actions on the reproductive tract. As hormones such as estradiol and progesterone modulate the incidence of substance abuse disorders in women, it is important to consider the influence HCs have on the female brain and behavior. This experiment explores how female sex steroid hormonal states associated with the rat estrous cycle, and modulating those states with HCs, influences measures of drug preference and responsivity. First, rats underwent food-light Pavlovian conditioning to measure conditioned orienting, a known predictor of amphetamine (AMP) place preference. Then, rats were conditioned and tested for AMP place preference with either an HC-implant or during estrous cycle stages associated with different ovarian hormone levels (i.e., proestrus (P) or metestrus/diestrus (M/D) while recording ultrasonic vocalizations (USVs) as an index of hedonic responsivity. Because of dopamines (DA) role in modulation of AMP actions, DA cell activity and availability were examined using tyrosine hydroxylase and FOS immunohistochemistry after final AMP challenge. Conditioned orienting did not differ between cycling and HC-implanted. P rats emitted more USVs during conditioning, showed higher AMP place preference throughout testing, and had higher DA cell activity in the substantia nigra compared to M/D and HC-implanted rats. Sex steroid hormone serum concentration and uterine horn thickness predicted some but not all of these measures. This experiment suggests ovarian hormones affect drug preference and responsivity, while providing novel insight into how hormone-altering contraceptives may reduce these measures.

animal behavior and cognition↗

bioRxiv2020

Prenatal exposure to EDCs dis-integrates and reconstitutes neuromolecular-behavioral relationships in adult rats

AO_SCPLOWBSTRACTC_SCPLOWExposure to endocrine-disrupting chemicals (EDCs) is ubiquitous in all species, including humans. Previous studies have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs [polychlorinated biphenyls (PCB), an industrial chemical mixture; vinclozolin (VIN), a fungicide], or vehicle. In adulthood, a sociosexual preference test (choice between hormone-primed and hormone-depleted opposite-sex rats) was administered. We profiled gene expression of in three brain regions involved in these behaviors [preoptic area (POA), medial amygdala (MeA), ventromedial nucleus (VMN)]. Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region (POA, MeA, VMN) had unique sets of genes altered in a sex- and EDC-specific manner. Sexually dimorphic gene expression disruption was particularly prominent for gene modules pertaining to sex steroid hormones and nonapeptides in the MeA. EDC exposure also changed the relationships between gene expression and behavior in the mate preference test, a pattern we refer to as dis-integration and reconstitution. These findings underscore the profound effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of mate preference behavior after prenatal exposure to EDCs.

neuroscience↗