Biology subjects

Olivier, J. D. A.

Publications and source records attributed to Olivier, J. D. A..

6 recordsLinked to original sources

bioRxiv2026

The serotonin transporter genotype x cumulative early-life stress interaction has opposite effects on anxiety-like behaviors in male and female rats

Early-life psychosocial adversity increases vulnerability to stress-related disorders and may begin as early as prior to conception via maternal stress. Consequently, early-life stress (ELS) in offspring may accumulate across early development. The short-allele variant of the serotonin transporter (SERT) gene has been implicated in depression risk and higher anxiety sensitivity following stress exposure, but for cumulative ELS it is unknown whether behavioral effects depend on the SERT genotype. In this study, we used heterozygous SERT knockout (SERT+/-) rats to model reduced SERT expression similar to human short-allele carriers. To investigate the effects of cumulative ELS on offspring behavioral phenotype, dams were exposed to stress before, during and after pregnancy, combined with offspring postnatal maternal separation. Cognitive, affective, and social behaviors were assessed in wild-type (WT) and SERT+/- (HET) male and female adults. Maternal care and anhedonia-like behaviors in dams were also assessed. Dams exposed to the cumulative stress (STR) displayed increased arched-back licking and grooming compared to controls (CTR). In the offspring, HET rats showed increased social investigation and tended to display hyperactivity compared to WT. Anxiety-like behavior was higher in HET females compared to WT females, with no genotype differences in males. Independent of genotype, STR rats consumed less sucrose and showed impaired object recognition compared to CTR; however, HET-STR rats performed better in the object recognition than WT-STR rats. A significant SERT genotype x cumulative ELS x sex interaction revealed opposing, sex-dependent effects on anxiety-like behavior. HET-STR females showed more anxiety-like responses relative to HET-CTR and WT-STR females, as well as HET-STR males. In contrast, HET-STR males were less anxious than HET-CTR and WT-STR males. Reduced SERT expression is linked to more social investigation alongside increased anxiety, particularly in SERT+/- females. While cumulative ELS did not induce robust anxiety-like and depressive-like phenotypes, overall, it impaired memory performance, an effect partially mitigated in SERT+/- rats. Notably, the SERT genotype differentially modulated anxiety-like behavior in male versus female offspring, increasing vulnerability in SERT+/- females while reducing it in SERT+/- males, an effect further amplified by exposure to cumulative ELS. These results underscore sex as a critical determinant in the interaction between genetic susceptibility and cumulative exposure to early adversity in shaping affective outcomes.

neuroscience↗

bioRxiv2025

Perinatal fluoxetine exposure increases male rat sexual behavior

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women due to their efficacy and safety profile, leading to potential exposure of the developing fetus and infant. Serotonin, which acts as a neurotransmitter in adults and is crucial for regulating male sexual behavior, also serves as a neurotrophic factor during early brain development. Yet, the long-term consequences of perinatal SSRI exposure on adult sexual functioning remain poorly understood. This study investigates the long-term effects of perinatal SSRI exposure on the sexual behavior of adult male rats in a seminatural environment. During pregnancy and lactating, mother rats were administered either fluoxetine (FLX, 10 mg/kg) or a control solution (CTR, 1% Methylcellulose) daily via oral gavage. Upon reaching adulthood, male offspring were assessed for sexual performance in a semi-natural setting, where they lived in mixed-sex groups for eight days. Comprehensive observations of sexual, social, and conflict behaviors were scoring from the first to the last copulatory behavior during the period in which female rats were sexually receptive. Our findings reveal that perinatal FLX exposure significantly increases sexual behavior in adult male rats, as evidenced by a higher total number of copulatory behaviors. This suggests that elevated serotonin levels during early development have enduring consequences for male rat sexual behavior in adulthood, potentially enhancing reproductive strategies and success in naturalistic environments.

neuroscience↗

bioRxiv2021

Male rat sexual behavior: insights from inter-copulatory intervals

The assessment of sexual behavior in male rats with the aim of unraveling underlying neurobiological mechanisms has in the recent decades been reduced to the annotation of mounts, intromissions and ejaculations. To provide a better understanding of the structure and patterns of copulation, it is necessary to extend and tailor the analysis to the natural organization of male rat copulation. This will lead to better formulation of hypotheses about neurobiological underpinnings of behavior. Mounts and intromissions are naturally organized in mount bouts consisting of one or more copulatory behaviors and are interspersed with time outs. We hypothesized that time outs and the post-ejaculatory interval (inter-copulatory intervals) are related and possibly under the control of a common copulatory inhibition mechanism that is the result of penile sensory stimulation. To test this hypothesis, we analyzed sexual behavior in male rats of three different cohorts from three different laboratories. Results showed that the post-ejaculatory interval and mean time out duration are strongly correlated in all cohorts analyzed. In addition, we showed that individual time out duration is at least partially predicted by the sum of sensory stimulation of copulatory components in the preceding mount bout, with more penile stimulation associated with longer time outs. These findings suggest that both time out and post-ejaculatory interval duration may be determined by the magnitude of sensory stimulation, which inhibits copulation. Whether the same neural pathways are involved in the central orchestration of both time outs and the post-ejaculatory interval should be subject to future studies.

neuroscience↗

bioRxiv2020

Perinatal exposure to fluoxetine and maternal adversity affect myelin-related gene expression and epigenetic regulation in the corticolimbic circuit of juvenile rats

Many pregnant women experience symptoms of depression, and are often treated with selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine. In utero exposure to SSRIs and maternal depressive symptoms is associated with sex-specific effects on the brain and behavior. However, knowledge about the neurobiological mechanisms underlying these sex differences is limited. In addition, most animal research into developmental SSRI exposure neglects the influence of maternal adversity. Therefore, we used a rat model relevant to depression to investigate the molecular effects of perinatal fluoxetine exposure in male and female juvenile offspring. We performed RNA sequencing and targeted DNA methylation analyses on the prefrontal cortex and basolateral amygdala; key regions of the corticolimbic circuit. Perinatal fluoxetine enhanced myelin-related gene expression in the prefrontal cortex, while inhibiting it in the basolateral amygdala. SSRI exposure and maternal adversity interacted to affect expression of genes such as myelin-associated glycoprotein (Mag) and myelin basic protein (Mbp). We speculate that altered myelination reflects altered brain maturation. In addition, these effects are stronger in males than in females, resembling known behavioral outcomes. Finally, Mag and Mbp expression correlated with DNA methylation, highlighting epigenetic regulation as a potential mechanism for developmental fluoxetine-induced changes in myelination.

neuroscience↗

bioRxiv2019

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

In the Western world, 2-5% of pregnant women use selective serotonin reuptake inhibitor (SSRI) antidepressants. There is no consensus on the potential long-term neurodevelopmental outcomes of early SSRI exposure. Our aim was to determine whether there is an overall effect of perinatal SSRI exposure in animals on a spectrum of behavioral domains. After a comprehensive database search in PubMed, PsycINFO, and Web of Science, we included 99 publications. We performed nine meta-analyses and two qualitative syntheses corresponding to different behavioral categories, aggregating data from thousands of animals. We found evidence for reduced activity and exploration behavior (standardized mean difference (SMD) -0.28 [-0.38, -0.18]), more passive stress coping (SMD -0.37 [-0.52, -0.23]), and less efficient sensory processing (SMD -0.37 [-0.69, -0.06]) in SSRI-versus vehicle-exposed animals. No differences were found for anxiety (p=0.06), social behavior, learning and memory, ingestive- and reward behavior, motoric behavior, or reflex and pain sensitivity. Exposure in the period equivalent to the human third trimester was associated with the strongest effects. HighlightsO_LIPerinatal SSRI exposure in rodents alters outcomes in three behavioral domains. C_LIO_LIIt leads to reduced activity, passive stress coping, and weaker sensory processing. C_LIO_LIFemales are understudied but seem to be less vulnerable than males. C_LIO_LIEarly postnatal exposure in rodents leads to the largest effects on behavior. C_LIO_LIThis is equivalent to the third trimester of pregnancy in humans. C_LI

animal behavior and cognition↗

bioRxiv2019

Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure

SSRIs are commonly used to treat pregnant women with depression. However, SSRIs can cross the placenta and affect the development of the fetus. The effects of perinatal SSRI exposure, and especially the effects on social behavior, are still incompletely documented. This study first aims to investigate whether rats show prosocial behavior in the form of consolation behavior. Secondly, it aims to investigate whether perinatal SSRI exposure affects this prosocial behavior. At last, we investigate whether the behavior changed after the rats had been exposed to an additional white-noise stressor. Rat dams received 10 mg/kg/d fluoxetine (FLX) or vehicle (CTR) via oral gavage from gestational day 1 until postnatal day 21. At adulthood, the rat offspring were housed in four cohorts of 4 females and 4 males in a seminatural environment. As prosocial behaviors are more prominent after stressful situations, we investigated the behavioral response of rats immediately after natural aggressive encounters (fights). Additionally, we studied whether a stressful white-noise exposure would alter this response to the aggressive encounters. Our study indicates that CTR-female rats are able to show third party prosocial behavior in response to witnessing aggressive encounters between conspecifics in a seminatural environment. In addition, we showed that perinatal FLX exposure impairs the display of prosocial behavior in female rats. Moreover, we found no signs of prosocial behavior in CTR- and FLX-males after natural aggressive encounters. After white-noise exposure the effects in third party prosocial behavior of CTR-females ceased to exist. We conclude that female rats are able to show prosocial behavior, possibly in the form of consolation behavior. In addition, the negative effects of perinatal fluoxetine exposure on prosocial behavior could provide additional evidence that SSRI treatment during pregnancy could contribute to the risk for social impairments in the offspring.

animal behavior and cognition↗