Female rat sexual behavior is unaffected by perinatal fluoxetine exposure

Jan Hegstad,Patty T Huijgens,Danielle J Houwing,Jocelien D.A Olivier,Roy Heijkoop,Eelke M.S Snoeren

doi:10.1016/j.psyneuen.2020.104796

Jan Hegstad, Patty T Huijgens + Show 4 more

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https://doi.org/10.1016/j.psyneuen.2020.104796

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Abstract

Serotonin plays an important role in adult female sexual behavior, however little is known about the influence of serotonin during early development on sexual functioning in adulthood. During early development, serotonin acts as neurotrophic factor, while it functions as a modulatory neurotransmitter in adulthood. The occurrence of serotonin release, could thus have different effects on behavioral outcomes, depending on the developmental period in which serotonin is released. Because serotonin is involved in the development of the HPG axis which is required for puberty establishment, serotonin could also alter expression patterns of for instance the estrogen receptor ɑ (ERɑ).The aim of our study was to investigate the effects of increased serotonin levels during early development on adult female rat sexual behavior during the full behavioral estrus in a seminatural environment. To do so, rats were perinatally exposed with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10 mg/kg FLX) and sexual performance was tested during adulthood. All facets of female sexual behavior between the first and last lordosis (behavioral estrus), and within each copulation bout of the behavioral estrus were analyzed. Besides the length and onset of the behavioral estrus and the sexual behaviors patterns, other social and conflict behavior were also investigated. In addition, we studied the effects of perinatal FLX exposure on ERɑ expression patterns in the medial preoptic nucleus, ventromedial nucleus of the hypothalamus, medial amygdala, bed nucleus of the stria terminalis, and the dorsal raphé nucleus.The results showed that perinatal fluoxetine exposure has no effect on adult female sexual behavior. The behavioral estrus of FLX-females had the same length and pattern as CTR-females. In addition, FLX- and CTR-females showed the same amount of paracopulatory behavior and lordosis, both during the full behavioral estrus and the “most active bout”. Furthermore, no differences were found in the display of social and conflict behaviors, nor in ERɑ expression patterns in the brain. We conclude that increases in serotonin levels during early development do not have long-term consequences for female sexual behavior in adulthood.

Highlights

Serotonin (5-HT) plays an important role in many social behaviors, including sexual behavior
When the pattern of darts and hops was analyzed over the time course of the behavioral estrus, FLX-females showed no significant difference in pattern of time spent on (timebin x treatment: F(19,342) = 0.899, NS, Fig. 3B) and number of paracopulatory behaviors (timebin x treatment: F(19,342) = 1.055, NS, data not shown) as CTRfemales
When the number of mounts and intromissions were analyzed separately, it was found that the FLX-females received less mounts (timebin x treatment: F(19,342) = 2.356, p = 0.001) and intromissions (timebin x treatment: F(19,342) = 2.070, p = 0.006) in the burrow area than CTRfemales in the 30%–70% timebins, but these mounts and intromissions were partly received in the open area of the seminatural environment instead of in the burrow (Fig. S1)

Summary

Introduction

Serotonin (5-HT) plays an important role in many social behaviors, including sexual behavior. While 5-HT is mainly a modulatory neurotransmitter during adulthood, 5-HT acts as a neurotrophic factor during early brain development, regulating cell division, differentiation, migration, and synaptogenesis (Azmitia, 2001; Gaspar et al, 2003). Female sexual behavior is highly dependent on the estrous cycle, which is under regulation of the hypothalamic-pituitary-gonadal (HPG) axis. The principle of this axis is that the hypothalamus releases gonadotropin-releasing hormone (GnRH), which induces the pituitary to release follicle stimulating hormone (FSH) and luteal hormone (LH). The release of FSH and LH, in turn, stimulates the ovaries to release steroid hormones, like estrogen and progesterone (reviewed in (Snoeren, 2019)).

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