Institutional Scholarship :: Browsing by Subject "Nucleus accumbens"

Browsing by Subject "Nucleus accumbens"

Now showing 1 - 13 of 13

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 The results show that in the NAc core, the estrogen withdrawn group had significantly higher dopamine reuptake rates (Vmax) compared to the vehicle group, suggesting that postpartum estrogen withdrawal may increase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 Although no significant differences were found in dopamine release ([DAp]) among the treatment groups, the withdrawn group exhibited a trend towards increased [DAp] compared to the sustained and vehicle groups.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.
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.
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.
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.
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.
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.
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.
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
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.
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
The Shaping of Sex Behavior, Odor Perception, and Neural Activation by Sex Experience: The Role of the Bed Nucleus of the Stria Terminalis’s Projections to the Nucleus Accumbens
(2016) Williams, Alexis; Been, Laura
Research has demonstrated that drugs of abuse lead to changes in both behavior and in neural activation. Drugs of abuse activate the same reward pathway in the brain as natural rewards, such as sex behavior. In order to better understand drug addiction, it is important to study how behavior and the brain change in response to experience with natural rewards. In the model organism of the Syrian hamster, sex behavior depends critically on the processing of odors. The bed nucleus of the stria terminalis (BNST), the medial amygdala (ME), and the medial preoptic area (MPOA) all process conspecific odors that help guide and reward sex behavior. There is plasticity in this brain region, and in particular sexual experience has been shown to modify the BNST’s involvement in opposite sex odor preference. It is unclear whether the number of activated projections is modified by experience. Thus, this research investigated how sex experience may change the neural response to a sexual odor in BNST neurons that project to the nucleus accumbens (NAc) in male Syrian hamsters. Hamsters were divided into a group that received no sexual experience or into a group that received eight ten-minute sexual experiences with a female hamster. Both groups of hamsters were injected with a retrograde tracer, Cholera Toxin B (CTB), into the NAc. The groups were given an odor experience and sacrificed. Immunohistochemistry was used to visualize CTB as well as c-Fos, a measure of recent neuronal activity. However, the neurons were not able to be visualized due to a hypothesized problem with over-fixation of the tissue. The research demonstrated that the number of mounts, intromissions, ejaculations, and the efficiency rate (mounts/intromissions) did not significantly differ over repeated sexual experiences. Future work utilizing correct staining of the tissue will help provide an understanding of how experiences that occur as part of an individual's everyday life can change the brain's reward system and impact future behavior.
ΔFosB and the Nucleus Accumbens: Explanations for Peripartum Mood Disorders
(2019) Valentine, Alissa; Been, Laura
Current research fails to determine the underlying neurological explanations of peripartum mood disorder (PMD) and its many behavioral components. In particular, peripartum anxiety behavior has been found to have increased rates compared to depression-like behavior. Yet, research efforts continue to concentrate on understanding postpartum depression. This has led to a significant gap in current literature, and its inability to explain peripartum anxiety and PMD as a whole. Therefore, the present study focused on peripartum anxiety-like behavior, and its relationship with changes in nucleus accumbens (NAc) neuroplasticity, specifically the transcription factor ΔFosB. Utilizing a hormone-simulated pregnancy model, we assessed anxiety behaviors in 21 female mice using the Elevated Plus Maze and Open Field Test. Prior to behavioral testing, mice were injected with one of two viral vectors, leading either to inhibited or undisturbed ΔFosB accumulation. This allowed us to investigate how ΔFosB impacts the exhibition of peripartum anxiety. Our trends suggest that ΔFosB accumulation during pregnancy is most impactful on peripartum anxiety-like behavior, but estrogen withdrawal after delivery is more influential on the postpartum anxiety behavior phenotype. These results are the first step towards gaining a comprehensive understanding of PMD’s manifestation in the brain, and contributes to a growing body of literature supporting increased educational and diagnostic tools to respond to peripartum anxiety-related disorders.
ΔFosB Induction in D1 Versus D2 Dopamine Neurons in the Nucleus Accumbens Following a Hormone-Simulated Pregnancy: An Exploratory Study
(2018) Carson, Paige; Been, Laura
Postpartum mood disorders (PMD) are a worldwide health concern, yet the neurobiological etiology is still widely unknown. In the present study we replicated the hormone-simulated pregnancy method developed by Liisa Galea in a novel transgenic mouse model. This approach allowed us to measure long-term genomic changes in dopaminergic plasticity in medium spiny neurons (MSNs) within the nucleus accumbens (NAc) through the transcription factor ΔFosB. We used 16 ovariectomized female transgenic mice that had fluorescent reporter molecules coupled to either D1 or D2 receptor-containing neurons; this allowed us to differentially visualize the activity of ΔFosB in each of the neuronal subtypes following a hormone-simulated pregnancy. We found a significant increase in the expression of ΔFosB in D2-MSNs in the NAc core of hormone-withdrawn animals relative to hormone-sustained animals. These neurobiological changes did not correspond with measures of anxiety in either an Elevated Plus Maze or Open Field Test. Furthermore, we found no significant changes in ΔFosB expression in D2-MSNs in the NAc shell nor in D1-MSNs in the NAc core and shell. By further understanding the influence that hormonal changes throughout pregnancy have on neurological systems, we can identify the systems that may be involved in pathological cases to develop better and more direct treatment and diagnosis options for PMD.

Browsing by Subject "Nucleus accumbens"

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