Browsing by Author "Been, Laura"

Now showing 1 - 20 of 23
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    A novel method evaluating the effects of peripartum estrogen fluctuations on sleep
    (2020) Irvine, Abiola; Been, Laura
    Clinically, sleep disorders are prevalent during pregnancy with more sleep disruptions occurring from late pregnancy through the postpartum period. Although there are many physical demands associated with pregnancy and birth that may contribute to these sleep disruptions, an understudied possibility is that hormones are directly acting in the brain to disrupt sleep. In order to test the effects of pregnancy hormones on sleep we used a hormone simulated pregnancy model in Syrian hamsters. Using Ethovision XT software, we developed a method to measure sleep using actigraphy data gathered through behavioral video recordings. Using this method we found that long periods of inactivity correlate with sleep while prolonged periods of activity correlate with wakefulness, thus activity can be used as a proxy for sleep. Using these data, we found trends suggesting that estrogen withdrawal following birth decreases total sleep time compared to sustained estrogen treatment following birth. This is important because these findings suggest a new method to measure sleep and that the effects of pregnancy hormones on sleep should be further evaluated.
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    Blocking Oxytocin Receptors in the Dorsal Raphe Nucleus of Syrian Hamsters
    (2019) Pisch, Natalie; Been, Laura
    Almost 20% of women suffer from peripartum depression and/or anxiety which has negative ramifications for the health of both mother and baby. Despite the gravity of this public health problem, effective treatments are lacking due to an incomplete understanding of the complex neurobiological mechanisms of these conditions. Previous research suggests that the intense fluctuations of ovarian hormones that occur in pregnancy and postpartum may render women particularly vulnerable to mood disturbances in this period. In particular, changes in oxytocin signaling in the brain, mediated by estrogen and progesterone, may contribute to the etiology of peripartum depression and anxiety. Previous work from our lab found increases in oxytocin-producing neurons in the paraventricular nucleus (PVN) of the hypothalamus and oxytocin receptors in the dorsal raphe nucleus (DRN), as well as increased anxiety-like behavior following a hormone simulated pregnancy. Given these results, this experiment sought to examine the effects of blocking oxytocin receptors in the DRN on anxiety behavior following a hormone-simulated pregnancy. Results from this pilot study suggest that blocking oxytocin signaling with an oxytocin receptor antagonist in the DRN during the postpartum period may impact anxiety-like behavior in hamsters. Further research is necessary to confirm the effects of OTA in the DRN during the peripartum period, but these results suggest that oxytocin signaling could be an important mechanism in peripartum anxiety and a potential route for the development of treatments.
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    Differential Dopamine Dynamics in the Nucleus Accumbens Core and Shell during Postpartum Estrogen Withdrawal Assessed Using Fast Scan Cyclic Voltammetry
    (2024) Zhang, Zhongyin; Been, Laura
    This thesis examines the impact of postpartum estrogen withdrawal on dopamine dynamics within the nucleus accumbens (NAc) core and shell subregions using a Hormone Simulated Pregnancy (HSP) model in mice. Utilizing Fast Scan Cyclic Voltammetry (FSCV), the study compares dopamine release and reuptake in these subregions across different hormone conditions. The results show that in the NAc core, the estrogen withdrawn group had significantly higher dopamine reuptake rates (Vmax) compared to the vehicle group, suggesting that postpartum estrogen withdrawal may increase dopamine reuptake in this subregion. Although no significant differences were found in dopamine release ([DAp]) among the treatment groups, the withdrawn group exhibited a trend towards increased [DAp] compared to the sustained and vehicle groups. In contrast, no significant differences were observed in either [DAp] or Vmax values among the treatment groups in the NAc shell. These findings suggest that hormone fluctuations during the postpartum estrogen withdrawal state have different effects on dopamine dynamics in the NAc core and shell, potentially informing novel treatments for postpartum depression (PPD). This study offers new insights into the neuroendocrinological basis of maternal behaviors and mood disorders with implications for developing therapeutic strategies targeting the dopamine system.
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    Effects of Ventral Tegmental Area Estrogen Receptor Alpha Knockdown Following a Hormone Simulated Pregnancy on ∆FosB production in the Nucleus Accumbens
    (2024) Clayton, Willow; Been, Laura
    The peripartum period is characterized by extreme changes in cycling hormones such as estrogens and progesterone. During pregnancy, estradiol levels rise dramatically, but drop quickly following birth, creating an estrogen withdrawal state that is associated with changes in mood and affect in humans and rodents. The mesolimbic dopamine pathway comprises the Ventral Tegmental Area (VTA) and Nucleus Accumbens (NAc), both containing estrogen receptors. Alterations in dopamine release from the VTA to the NAc have been associated with changes in mood and affect and increased ΔFosB, a transcription factor implicated in reward and motivated behaviors, as well as that serves as a marker for long term neural plasticity. In order to better understand if and how estrogen receptors play a role in the expression of ∆FosB in the NAc following estrogen withdrawal this study used a viral mediated gene transfer approach to selectively silence ERa in the VTA. Then, following a hormone simulated pregnancy, ∆FosB was measured in the NAc using immunohistochemistry. Overall there was no significant effect of knocking down estrogen receptor alpha in the VTA on the expression of ∆FosB in the NAc following an HSP in either the estrogen withdrawn or sustained groups. Future directions will expand the number of subjects in the control groups in order to replicate past results which show a main effect of hormone condition. This would allow for a better understanding of the effects of estrogen receptor alpha knockdown on FosB expression in the VTA. Additionally, future studies, including a second part to the present study using a second cohort, will explore the possibility that estrogen receptor beta rather than alpha is required for the increased expression of ∆FosB in the NAc following an HSP.
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    Molecular Mechanisms Underlying Sexual Experience-Dependent Neuroplasticity of the Nucleus Accumbens after in Syrian Hamsters
    (2016) Sidibe, David; Been, Laura
    This study is an aims to clarify the role of delta fos-b in the reinforcement of sexual behavior in Syrian (Golden) hamsters. We used a one-way ANOVA to compare levels of delta fos-b expression from experienced animals to naïve animals, and males to females. Western blot analysis was used to quantify the amount of protein in both the nucleus accumbens (NAc) and the caudate (CP), a control brain area. We found a significantly greater amount of delta fos-b expression in the NAc in sexually experienced hamsters (both males and females) compared to naïve. In addition, there was no difference between sexually experienced males and females in overall delta fos-b expression in the NAc. Implications and future directions point towards further unraveling the unknown mechanisms of reinforcement of sexual behavior in hamsters through humans.
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    Naturally Motivated Behavior and Neuroplasticity: How Sexual Experience Affects Neural Activation During Sexual Behavior in Female Syrian Hamsters
    (2016) Caron, Madeline F.; Been, Laura
    Naturally motivated behaviors, like sexual behavior, are subject to behavioral plasticity, which can affect neuronal function. The purpose of this study was to investigate the plasticity of sexual behavior and neural circuits related to sexual behavior in female Syrian hamsters. We hypothesized that lordosis latency would decrease and lordosis duration would increase with sexual experience. We also hypothesized that sex experience would increase the activation of the projections from the prefrontal cortex (PFC) to the nucleus accumbens (NAc) during sexual behavior. We tested our hypothesis by ovariectomizing and hormone priming all subjects and giving half of the subjects six weeks of sex experience while the other half remained sexually naïve. All subjects then received an injection of a retrograde tracer into their NAc and a final sexual experience. All subjects were then sacrificed, and their brain tissue was collected and stained using immunohistochemical techniques. Our data did not support our hypotheses about lordosis latency or duration, and we were unable to test our neuroplasticity hypothesis due to unquantifiable staining. Limitations and possible troubleshooting techniques are discussed in the context of directions for future research.
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    Neuroplasticity after Sexual Experience in the Nucleus Accumbens of Syrian hamsters
    (2016) Acabá, Luis; Been, Laura
    Research over the past three decades has demonstrated that many neural changes occur in response to rewarding stimuli and behavior. However, most of this research has focused on the changes that occur following drug use and their role in addiction. Less research has investigated the neural changes in response to everyday rewarding behaviors such as eating, exercising, and sexual behavior, and even less has explored whether these changes differ in male and female brains. The goal of this study was to investigate the changes in brain circuitry that occur in Syrian hamsters after exposure to sexual experiences and to identify any possible sex differences involved. Specifically, levels of delta FosB, a transcription factor that is important for long-term neural plasticity following rewarding experiences, was measured in the Nucleus Accumbens (NAc) as a way to quantify these neural changes. This study also aimed at investigating whether the efficiency with which hamsters mate is improved with experience, as measured by the time the hamsters are actively having sex and the amount of sex-related behaviors they perform. It was expected that sexual experiences would lead to an up-regulation of delta FosB in the NAc, that this up-regulation would not differ between the sexes, and that mating efficiency would improve with experience. The results demonstrated that sexual experience led to higher delta FosB levels in the NAc than controls, and that there were no differences in delta FosB levels between males and females of the same group. This study also found that mating efficiency was not improved with experience. The results obtained in this study suggest that the normal rewarding behavior of sexual experience leads to neuroplastic changes in the NAc of Syrian hamsters and that male and female Syrian hamsters likely have similar neuroplastic changes following sexual experiences. This research has the potential to provide a better understanding of how drugs of abuse take advantage of reward pathways, and eventually lead to better treatments for addiction.
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    Oxytocin Receptor Plasticity Following a Hormone-Simulated Pregnancy in Syrian Hamsters: Implications for Postpartum Mood Disorders
    (2018) Benedetto, Lauren E.; Been, Laura
    Despite the fact that approximately 15‒20% of women develop postpartum depression and/or anxiety, and that the resulting outcomes for both the mother and her child are negative, the underlying neurobiological mechanisms of the disorders remain poorly understood. Previous research suggests that ovarian hormone fluctuations as well as changes in oxytocin signaling that occur at parturition and in the postpartum likely play a role in the etiology of these disorders. Given the increase in oxytocin-producing neurons in the paraventricular nucleus (PVN) of the hypothalamus following a hormone simulated pregnancy, Experiment 1 sought to examine oxytocin receptor levels in PVN efferents, particularly in the medial amygdala (MeA), nucleus accumbens (NAc), bed nucleus of the stria terminalis (BNST), and raphe nuclei. Results indicate an increase in oxytocin receptor density in the raphe nuclei among hormone-withdrawn animals as compared to controls, suggesting that the region could be implicated in the etiology of anxiety-like behavior during the postpartum period. Unexpectedly, behavioral results indicate reduced non-specific locomotor ability as measured by the Open Field Test and increased anxiety-like behavior as measured by the Elevated Plus Maze in hormone-withdrawn animals. Experiment 2 sought to explore whether neurodegeneration was responsible for the decreased oxytocin-producing neurons found in hormone-sustained animals. Unexpectedly, cell death is visible in hormone-withdrawn and not hormone-sustained animals, suggesting that some neuroplasticity may be taking place. Overall, these two experiments add to our understanding of the brain and behavior following hormone-simulated pregnancy in hamsters, which may inform our understanding the postpartum period in humans.
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    Plasticity of Oxytocin Receptors in the Postpartum Period Using a Hamster Model
    (2018) Taveras, Shantal; Been, Laura
    The deleterious consequences of postpartum depression and anxiety (PPD) on the mother-child dyad has greatly incentivized more research in the neurobiological mechanisms during the peripartum period. Several studies have stipulated that neurobiological and hormonal components may lead to the etiology of PPD. However, a greater understanding of the complexities of PPD will not unfold until knowledge on the typical patterns of puerperium is prioritized. In the current study, we simulated pregnancy in a hamster model to investigate changes in oxytocin receptor density in the efferents of the paraventricular nucleus (PVN). For the four regions of interest, we predicted a decrease in oxytocin receptors density for the estrogen-withdrawn hamsters within the postpartum period. The raphe nucleus (RN) was the only region of interest that attained statistical significance. Contrary to our hypothesis, the estrogen-withdrawn group exhibited a significant increase of oxytocin receptors compared to the control group in this region. Utilizing an open field test and elevated plus maze, we also expected to observe less anxiety-like behaviors from the estrogen-withdrawn group. However, our results did not reveal any statistical significance for anxiety-like behaviors. Following previous results, this study also investigated the overall neurodegeneration within the PVN, specifically an increase of cell-death in the estrogen-sustained group. After qualitative analysis, we visualized greater fluoro-jade staining, a measure of neurodegeneration, within the estrogen-withdrawn group. By gaining greater comprehension of the estrogen and oxytocin pathway, it will lead to a greater understanding of the typical postpartum period and, thereby, the intricacies involved in the peripartum period.
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    Postpartum Oxytocin Receptor Plasticity And Anxiety-Like Behavior in Syrian Hamsters: The Potential Role of the Dorsal Raphe Nuclei
    (2018) Levine, Taylor; Been, Laura
    The postpartum period is a time of high vulnerability for females to develop depression. Not only does postpartum depression significantly hinders the motivation and enjoyment that a mother feels in her new role, but also the development of the offspring, doubling the impact of this unique affective disorder. Oxytocin, a hormone involved in birth, maternal behavior, depression, and anxiety may help to untangle the link between postpartum hormonal levels and the occurrence of postpartum depression. The present study examined oxytocin receptor plasticity in efferents of the paraventricular nucleus, the main source of central oxytocin, in an animal model following a hormone-simulated pregnancy. Estrogen-withdrawn females exhibited a significantly greater density of oxytocin receptors in the dorsal raphe nuclei and there were no significant differences in receptor density between hormonal treatment groups in other efferents examined. Estrogen-withdrawn females also displayed higher levels of anxiety-like behavior than estrogen-sustained animals in the Elevated Plus Maze. Ultimately, the present study aimed to understand the role of oxytocin signaling in postpartum mood disturbances and how oxytocin may meet the demand as a novel, targeted treatment for postpartum depression.
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    Postpartum oxytocin receptor plasticity in Syrian hamsters: Implications for the treatment of peripartum mood disorders
    (2018) Heaton, Elizabeth C.; Been, Laura
    Peripartum mood disorders, if left untreated, result in negative outcomes for both the mother and child. Despite these severe consequences, the neurobiology of peripartum mood disorders is not well understood. The present study aims to build upon previous research investigating the role of oxytocin in neuroplastic and behavioral changes during the peripartum period. Past work found a significant increase in oxytocin-immunoreactive neurons in the PVN as a result of hormone withdrawal in a hormone-simulated pregnancy model conducted in Syrian hamsters. Using the same model, we studied post-synaptic plasticity: specifically, we assessed which PVN efferents, if any, experienced changes in oxytocin receptor expression using receptor autoradiography. The regions of interest in this study were medial amygdala (MA), nucleus accumbens (NA), bed nucleus of the stria terminalis (BNST), and the raphe nuclei as each of these four areas are heavily involved in the production of maternal behavior. There was a significant increase in OTR density in the dorsal raphe in the hormone withdrawn group as compared to oil control. Changes in OTR density in the dorsal RN, which regulates serotonergic activity and anxiety- and depression-related behavior in humans and rodents, may play a role in the development or sustainment of peripartum mood disorders.
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    The Effects of Peripartum Estradiol Fluctuations on Mesolimbic Dopamine Dynamics
    (2023) Halliday, Amanda R.; Been, Laura
    The peripartum period involves dramatic hormonal changes; estradiol levels increase 10-100 fold during pregnancy and drop to pre-pregnancy levels immediately following expulsion of the placenta. These drastic fluctuations are believed to play a role in peripartum mood and anxiety disorders, which affect approximately 1 in 8 birthing people. It is likely that changes to ovarian/placental hormone levels affect the mesolimbic pathway, which is an important pleasure and motivation center in the brain. However, specific mechanisms connecting estradiol fluctuations to mood and behavioral changes are not well understood. We used fast-scan cyclic voltammetry (FSCV) to characterize the effects of a hormone-simulated pseudopregnancy (HSP) on mesolimbic dopamine dynamics in female C57BL/6 mice. We found that high-dose estradiol administration during the HSP decreases dopamine release and reuptake rate in the nucleus accumbens (NAc) core. Further research will aim to supplement these findings and draw more clear connections between peripartum estradiol fluctuations, mesolimbic dopamine dynamics, and affective/behavioral changes.
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    The Effects of Postpartum Estrogen and Progesterone Withdrawal on ΔFosB Expression in the Nucleus Accumbens and Anxiety- and OCD-like Behaviors in Mice
    (2022) Mercado, Sophia; Been, Laura
    Anxiety and OCD are debilitating psychiatric conditions characterized by somatic, cognitive, and or behavioral symptoms that occur in anticipation of potential threats. These symptoms result from the abnormal processing of fear- or stress-provoking stimuli and alterations in brain regions responsible for motivated behaviors. Anxiety and related disorders are seen with increased prevalence during the peripartum period, which refers to the period before, during, and after pregnancy (Forray et al., 2010). Most of the literature on the emergence and exacerbation of psychiatric conditions during the peripartum period focuses on depression. As a result, there is a lack of research on anxiety and OCD during the peripartum period and the neurobiological underpinnings of these disorders. The present study used a hormone stimulated pregnancy (HSP) model in female mice to assess the effects of estradiol-withdrawal on anxiety-like and OCD-like behaviors in mice and the induction of a transcription factor implicated in compulsive-like behaviors, ΔFosB, in the nucleus accumbens (NAc), the prime brain region in regulating motivated behaviors. In addition, the present study employed a novel HSP regimen that more accurately reflects the trajectory of progesterone during human pregnancy. We found that there were no differences in anxiety- or OCD-like behavior in mice in the hormone-sustained versus hormone-withdrawn groups, however the hormone-sustained group in the modified HSP cohort exhibited greater ΔFosB induction in the NAc core. These findings suggest that progesterone influences the estradiol-withdrawal-mediated induction of ΔFosB in this region.
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    The Impact of Peripartum Estrogen Withdrawal on Dopamine Dynamics in the Nucleus Accumbens Core and Shell in Mice
    (2024) Courtney, May; Been, Laura
    The peripartum period refers to the time before, during, and after parturition, which is the act of childbirth. Significant fluctuations in hormones occur during the peripartum period. In placental mammals, estradiol levels increase up to 100-fold during late-pregnancy and drop rapidly and immediately after parturition. This withdrawn estrogen state is believed to be involved with the neurobiological mechanisms that result in postpartum mood and anxiety disorders, which impacts roughly one in seven birthing people. Previous research has shown that estradiol withdrawal impacts the nucleus accumbens (NAc) along with motivated behaviors. However, the exact neural mechanisms that connect estradiol hormonal changes to changes in behavior are not well understood. To better understand how peripartum estrogen fluctuations impact the NAc, a hormone simulated pregnancy (HSP) was used in adult female C57BL/6 mice to model the estradiol withdrawal state and dopamine dynamics were characterized in the nucleus accumbens core (NAcC) and shell (NAcSh) using the electrochemical technique of ex-vivo fast scan cyclic voltammetry (FSCV). The results showed increased dopamine release and reuptake in the NAcC in the estrogen-withdrawn group. Dopamine release and reuptake did not vary across treatment groups in the NAcSh. Thus, these findings indicate that postpartum estrogen withdrawal does impact dopamine dynamics in the NAcC but not in the NAcSh
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    The Impact of Progesterone and Estrogen Withdrawal via a Hormone-simulated Pseudopregnancy Model on ΔFosB Expression in the Nucleus Accumbens and Anxiety- and Compulsive-like Behavior in Female Mice
    (2022) Corbin, Jaclyn; Been, Laura
    Throughout pregnancy, ovarian hormones fluctuate dramatically. The rapid decrease of estradiol and progesterone during birth specifically have been implicated in a variety of mood and anxiety disorders. The current study investigates the effects of hormone withdrawal on changes in anxiety-like and OCD-like behaviors by using an old and modified hormone simulated pseudopregnancy (HSP) model in C57Bl/6 adult female mice. These models involved ovariectomized mice and providing daily hormone injections of either estradiol or estradiol and progesterone to mimic the hormones produced during pregnancy and the postpartum period. Of the mice only receiving estradiol (n=16), they were split into two groups based on whether or not they continued to receive estradiol injections throughout the postpartum period. Similarly, the subjects receiving estradiol and progesterone were also split into two groups (n=14) based on whether or not they continued to receive estradiol and progesterone or not throughout the postpartum period. It was hypothesized that the animals that stopped receiving hormone injections in the postpartum period would display more anxious behavior in an open field test and elevated plus maze test. It was also predicted that these animals would display more compulsive-like behavior in a marble burying assay. Researchers examined ΔFosB, a marker of neural plasticity within the nucleus accumbens (NAc), a brain region implicated in mood and anxiety disorders, to determine correlations between the NAc, hormone fluctuations, and behavior. We hypothesized that we would see a correlation between increased anxiety and compulsive-like behavior in the hormone withdrawn mice with increased ΔFosB expression in the NAc. There was no significant impact of hormone withdrawal on behavioral assays, but there was a significant increase in ΔFosB expression in the NAc core of estradiol and progesterone sustained mice. There were also significant increases in locomotion in the groups receiving hormones throughout the postpartum period. Future research should focus on the role of ΔFosB expression in mood disorders related to the postpartum period using this new HSP model.
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    The Impact of Sexual Experience On Sexual Behavior and Neural Activation in Female Syrian Hamsters
    (2016) Walsh, Olivia; Been, Laura
    Natural rewards and drug reinforcement cause an increase in frequency in motivated behaviors that are aimed at obtaining different rewards. These changes in behavior are reflecting changes in neurobiology. The majority of past research examining motivated behaviors has focused on investigating how addictive drugs affect the brain’s reward pathway, particularly the prefrontal cortex – nucleus accumbens reward pathway. By understanding how the reward pathway functions to regulate the behaviors it evolved for, researchers may be able to better understand how this pathway is activated under pathological conditions and improve treatment. The present study aims to observe 1) how sex experience changes sex behavior; and 2) how sex experience affects the prefrontal cortex – nucleus accumbens reward pathway in female Syrian hamsters. The first prediction is that there will be a decrease in lordosis times and an increase in lordosis duration times across the repeated sexual experiences. The second prediction is that there will be a significant increase in the activation of neuronal projections in the prefrontal cortex – nucleus accumbens reward pathway in the sexually experienced group. The results showed no statistically significant differences in lordosis latency and duration across the seven sexual experiences. This lack of significance may have been due to an interaction between the male and females during sexual behavior that was not measured for, such as ultrasonic sounds. Due to a lack of quantifiable staining, the second hypothesis was not able to be tested. However, it will be interesting to see if there were still changes in neurobiology even though there were not changes in behaviors. By understanding how these naturally motivated behaviors activate the reward pathway, researchers may be able to better understand the neural causation of pathologies of motivation, such as addiction.
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    The Neurobiological Etiology of Postpartum Depression: The Role of Oxytocin in the Hypothalamus and the Amygdala
    (2017) Bodie, Clio; Been, Laura
    In the current study, we simulated the hormonal conditions of pregnancy and a postpartum period in a Syrian hamster model in order to better understand the neurobiological etiology of postpartum depression (PPD). PPD is a distinct subtype of major depressive disorder, which develops in new mothers during the first few weeks after delivery. It is a prevalent disorder and has incredibly harmful effects on both the mother and her infant, but not much is understood about its etiology, which makes treatment difficult. We hypothesized that after estrogen withdrawal produced a PPD-like state, subjects would show behavioral indicators of anhedonia through the Sucrose Preference Test. We also expected to find decreased levels of oxytocin producing cells in the paraventricular nucleus of the hypothalamus (PVN) and the medial amygdala of animals that experienced hormone withdrawal, which we believed might contribute to the development of PPD. We did not find any significant differences in the behavioral measures testing anhedonia. Our neurobiological findings were the opposite of what we hypothesized- we found significantly higher quantities of oxytocin producing neurons in the PVN of hamsters that experienced hormone withdrawal. These findings may indicate that oxytocin contributes to dysregulation of the HPA axis in the postpartum or that oxytocin fluctuations within the postpartum period affect PPD. Future research should further explore the role of oxytocin in the hypothalamus and amygdala, as it appears to be associated with PPD.
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    The Neurobiological Mechanisms of Postpartum Depression: Observing Oxytocin’s Role in the Paraventricular Nucleus of the Hypothalamus Using a Hamster Model
    (2017) Lee, Rachel H.; Been, Laura
    Postpartum depression is a condition that affects new mothers’ cognition and behavior, as well as her ability to raise the child. It affects up to 15% of women who give birth and has a wide variety of symptoms. Despite its prevalence and severity, though, the neurobiological mechanisms underlying the condition remain understudied. During pregnancy and postpartum, dramatic hormone changes occur and may play a key role in the neurobiological and behavioral aspects in postpartum depression – of note is the rise in ovarian hormones followed by their sudden drop after giving birth. Current research also suggests that the dysregulation of the hormone oxytocin (OXT), which is synthesized in the paraventricular nucleus of the hypothalamus (PVH) and medial amygdala (MA), underlies the onset of postpartum depression. We modeled the postpartum hormonal changes in a hamster model, and specifically looked for changes in OXT-producing neurons in the PVH and MA using an immunohistochemical reaction. During behavioral testing, we hypothesized that hormone withdrawn animals would show a decreased preference for sugar water, and during immunohistochemistry, we hypothesized that this same group would show a significantly lower count of OXT cells, while control animals would show a significantly higher count. Interestingly, results showed the opposite of what we predicted – hormone withdrawn animals had a significantly higher count of OXT cells and vice versa. These results contain implications for potential fluctuations of OXT levels within the postpartum period itself.
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    The Neurobiological Mechanisms of Postpartum Depression: The Role of Oxytocin in the Hypothalamus and Amygdala
    (2017) Amaral, Claudia F.; Been, Laura
    Although postpartum depression has a prevalence of approximately 15% and can result in negative outcomes for both the mother and her child, its underlying neurobiological mechanisms remain mostly unknown. Previous research suggests that ovarian hormone fluctuations that occur during the postpartum period could underlie depressive symptoms in postpartum depression. Studies have also suggested that changes in oxytocin signaling could also play a role in the etiology of this disorder. The present study adapts the ovarian withdrawal model of postpartum depression to a Syrian hamster animal model in order to study the neurobiological mechanisms of postpartum depression. Its aim is to test whether hormone withdrawal during the postpartum period results in changes in oxytocin signaling between the paraventricular nucleus and the medial amygdala. It is hypothesized that these neurobiological changes could be implicated in depressive-like behavior during the postpartum period.
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    The Role of Mesolimbic Estrogen Receptors in Modulating Peripartum Estradiol Withdrawal Effects on Neuroplasticity
    (2024) Barrett, Annie; Been, Laura
    Postpartum Depression (PPD) has many biological and sociocultural contributors as well as significant implications. One biological contributor is the fluctuation in peripartum hormones, particularly the significant increase in estradiol during pregnancy, followed by a rapid decrease following childbirth, known as postpartum estradiol withdrawal. These hormone changes impact the mesolimbic dopamine pathway, which consists of dopaminergic projections from the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc). Recent evidence has shown that Estrogen Receptors (ERs) in the VTA may mediate this relationship between estradiol withdrawal and mesolimbic dopamine transmission. These changes may be measured by ΔFosB, a transcription factor in the NAc that is associated with long-term neuroplasticity and has implications for depressive-like behaviors in rodent models. We silenced ERs in the VTA using a stereotaxic injection of lentiviruses carrying short-hairpin RNA (shRNA), then we used a hormone-simulated pseudopregnancy (HSP) method to simulate the estradiol and progesterone changes during pregnancy. Finally, we used an immunohistochemistry protocol to determine the role of ERs in the VTA in modulating the effect of postpartum estradiol withdrawal on ΔFosB levels in the NAc in adult female C57BL/6 mice. We found no significant effects of the virus condition, hormone condition, or the interactions between virus and hormone conditions in the NAc Core or Shell. This study will be concluded this summer to include more scrambled control animals and a study of ESR2 knockdown. Future research would differentiate between the injected and non-injected side of the brain, and may consider interactions between ERɑ and ERβ and behavioral implications. Keywords: neuroplasticity, postpartum depression, estrogen receptors, hormone-simulated pseudopregnancy, ventral tegmental area, nucleus accumbens