@article{duque-wilckens_teis_sarno_stoelting_khalid_dairi_douma_maradiaga_hench_dharshika_et al._2022, title={Early life adversity drives sex-specific anhedonia and meningeal immune gene expression through mast cell activation}, volume={103}, url={http://dx.doi.org/10.1016/j.bbi.2022.03.009}, DOI={10.1016/j.bbi.2022.03.009}, abstractNote={Exposure to early life adversity (ELA) in the form of physical and/or psychological abuse or neglect increases the risk of developing psychiatric and inflammatory disorders later in life. It has been hypothesized that exposure to ELA results in persistent, low grade inflammation that leads to increased disease susceptibility by amplifying the crosstalk between stress-processing brain networks and the immune system, but the mechanisms remain largely unexplored. The meninges, a layer of three overlapping membranes that surround the central nervous system (CNS)- dura mater, arachnoid, and piamater – possess unique features that allow them to play a key role in coordinating immune trafficking between the brain and the peripheral immune system. These include a network of lymphatic vessels that carry cerebrospinal fluid from the brain to the deep cervical lymph nodes, fenestrated blood vessels that allow the passage of molecules from blood to the CNS, and a rich population of resident mast cells, master regulators of the immune system. Using a mouse model of ELA consisting of neonatal maternal separation plus early weaning (NMSEW), we sought to explore the effects of ELA on sucrose preference behavior, dura mater expression of inflammatory markers and mast cell histology in adult male and female C57Bl/6 mice. We found that NMSEW alone does not affect sucrose preference behavior in males or females, but it increases the dura mater expression of the genes coding for mast cell protease CMA1 (cma1) and the inflammatory cytokine TNF alpha (tnf alpha) in females. When NMSEW is combined with an adult mild stress (that does not affect behavior or gene expression in NH animals) females show reduced sucrose preference and even greater increases in meningeal cma1 levels. Interestingly, systemic administration of the mast cell stabilizer Ketotifen before exposure to adult stress prevents both, reduction in sucrose preference an increases in cma1 expression in NMSEW females, but facilitates stress-induced sucrose anhedonia in NMSEW males and NH females. Finally, histological analyses showed that, compared to males, females have increased baseline activation levels of mast cells located in the transverse sinus of the dura mater, where the meningeal lymphatics run along, and that, in males and females exposed to adult stress, NMSEW increases the number of mast cells in the interparietal region of the dura mater and the levels of mast cell activation in the sagittal sinus regions of the dura mater. Together, our results indicate that ELA induces long-term meningeal immune gene changes and heightened sensitivity to adult stress-induced behavioral and meningeal immune responses and that these effects could mediated via mast cells.}, journal={Brain, Behavior, and Immunity}, publisher={Elsevier BV}, author={Duque-Wilckens, Natalia and Teis, Robert and Sarno, Erika and Stoelting, Frauke and Khalid, Sonia and Dairi, Zakaria and Douma, Alex and Maradiaga, Nidia and Hench, Stina and Dharshika, Christine D. and et al.}, year={2022}, month={Jul}, pages={73–84} }
 @article{gao_duque-wilckens_aljazi_moeser_mias_robison_zhang_he_2022, title={Impaired KDM2B-mediated PRC1 recruitment to chromatin causes defective neural stem cell self-renewal and ASD/ID-like behaviors}, volume={25}, url={http://dx.doi.org/10.1016/j.isci.2022.103742}, DOI={10.1016/j.isci.2022.103742}, abstractNote={Recent clinical studies report that chromosomal 12q24.31 microdeletions are associated with autism spectrum disorder (ASD) and intellectual disability (ID). However, the causality and underlying mechanisms linking 12q24.31 microdeletions to ASD/ID remain undetermined. Here we show Kdm2b, one gene located in chromosomal 12q24.31, plays a critical role in maintaining neural stem cells (NSCs) in the mouse brain. Loss of the CxxC-ZF domain of KDM2B impairs its function in recruiting Polycomb repressive complex 1 (PRC1) to chromatin, resulting in de-repression of genes involved in cell apoptosis, cell-cycle arrest, NSC senescence, and loss of NSC populations in the brain. Of importance, the Kdm2b mutation is sufficient to induce ASD/ID-like behavioral and memory deficits. Thus, our study reveals a critical role of KDM2B in normal brain development, a causality between the Kdm2b mutation and ASD/ID-like phenotypes in mice, and potential molecular mechanisms linking the function of KDM2B-PRC1 in transcriptional regulation to the 12q24.31 microdeletion-associated ASD/ID.}, number={2}, journal={iScience}, publisher={Elsevier BV}, author={Gao, Yuen and Duque-Wilckens, Natalia and Aljazi, Mohammad B. and Moeser, Adam J. and Mias, George and Robison, Alfred J. and Zhang, Yi and He, Jin}, year={2022}, month={Feb}, pages={103742} }
 @article{duque-wilckens_trainor_2022, title={Oxytocin release in stressful times}, volume={140}, url={http://dx.doi.org/10.1016/j.psyneuen.2022.105709}, DOI={10.1016/j.psyneuen.2022.105709}, journal={Psychoneuroendocrinology}, publisher={Elsevier BV}, author={Duque-Wilckens, Natalia and Trainor, Brian C.}, year={2022}, month={Jun}, pages={105709} }
 @article{peen_duque-wilckens_trainor_2021, title={Convergent neuroendocrine mechanisms of social buffering and stress contagion}, volume={129}, url={http://dx.doi.org/10.1016/j.yhbeh.2021.104933}, DOI={10.1016/j.yhbeh.2021.104933}, abstractNote={Social interactions play a key role in modulating the impact of stressful experiences. In some cases, social interactions can result in social buffering, the process in which the presence of one individual reduces the physiological and behavioral impact of stress in another individual. On the other hand, there is growing evidence that a key initiating factor of social buffering behaviors is the initiation of an anxiogenic state in the individual that was not directly exposed to the stress. This is referred to as stress contagion (a form of emotion contagion). Both processes involve the transmission of social information, suggesting that contagion and buffering could share similar neural mechanisms. In general, mechanistic studies of contagion and buffering are considered separately, even though behavioral studies show that a degree of contagion is usually necessary for social buffering behaviors to occur. Here we consider the extent to which the neuropeptides corticotropin releasing hormone and oxytocin are involved in contagion and stress buffering. We also assess the importance that frontal cortical areas such as the anterior cingulate cortex and infralimbic cortex play in these behavioral processes. We suggest that further work that directly compares neural mechanisms during stress contagion and stress buffering will be important for identifying what appear to be distinct but overlapping circuits mediating these processes.}, journal={Hormones and Behavior}, publisher={Elsevier BV}, author={Peen, Natanja F. and Duque-Wilckens, Natalia and Trainor, Brian C.}, year={2021}, month={Mar}, pages={104933} }
 @article{minie_petric_ramos-maciel_wright_trainor_duque-wilckens_2021, title={Enriched laboratory housing increases sensitivity to social stress in female California mice (Peromyscus californicus)}, volume={241}, url={http://dx.doi.org/10.1016/j.applanim.2021.105381}, DOI={10.1016/j.applanim.2021.105381}, abstractNote={Domesticated mice and rats have shown to be powerful model systems for biomedical research, but there are cases in which the biology of species is a poor match for the hypotheses under study. The California mouse (Peromyscus californicus) has unique traits that make it an ideal model for studying biological mechanisms underlying human-relevant behaviors such as intra-female aggression, biparental care, and monogamy. Indeed, peer-reviewed scientific publications using California mouse as a model for behavioral research have more than doubled in the past decade. Critically, behavioral outcomes in captive animals can be profoundly affected by housing conditions, but there is very limited knowledge regarding species-specific housing needs in California mice. Currently, California mouse investigators have to rely on guidelines aimed for more common laboratory species that show vastly different physiology, behavior, and/or ecological niche. This not only could be suboptimal for animals' welfare, but also result in lack of standardization that could potentially compromise experimental reproducibility and replicability across laboratories. With the aim of assessing how different housing systems can affect California mouse behavior both in the home cage as well as the open field and social interaction tests before and after social defeat stress, here we tested three different caging systems: 1. Standard mouse cage, 2. Large cage, and 3. Large cage + environmental enrichment (EE), which focused on increasing vertical complexity based on observations that California mice are semiarboreal in the wild. We found that the effects of housing were largely sex specific: compared to standard cages, in females large + EE reduced home cage stereotypic-like backflipping and rearing behaviors, while large cage increased social interactions. In males, the large+EE cage reduced rearing and digging but did not significantly affect backflipping behavior. Interestingly, while there were no significant differences in the open field and social interaction pre-stress behaviors, large and large+EE housing increased the sensitivity of these tests to detect stress induced phenotypes in females. Together, these results suggest that increasing social and environmental complexity affects home cage behaviors in male and female California mice without interfering with, but rather increasing the magnitude of, the effects of defeat stress on the open field and social interaction tests.}, journal={Applied Animal Behaviour Science}, publisher={Elsevier BV}, author={Minie, Vanessa A. and Petric, Radmila and Ramos-Maciel, Stephanie and Wright, Emily C. and Trainor, Brian C. and Duque-Wilckens, Natalia}, year={2021}, month={Aug}, pages={105381} }
 @article{gao_duque-wilckens_aljazi_wu_moeser_mias_robison_he_2021, title={Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors}, volume={4}, url={http://dx.doi.org/10.1038/s42003-021-02282-z}, DOI={10.1038/s42003-021-02282-z}, abstractNote={AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.}, number={1}, journal={Communications Biology}, publisher={Springer Science and Business Media LLC}, author={Gao, Yuen and Duque-Wilckens, Natalia and Aljazi, Mohammad B. and Wu, Yan and Moeser, Adam and Mias, George and Robison, Alfred J. and He, Jin}, year={2021}, month={Jun} }
 @article{duque-wilckens_torres_yokoyama_minie_tran_petkova_hao_ramos-maciel_rios_jackson_et al._2020, title={Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance}, volume={117}, url={http://dx.doi.org/10.1073/pnas.2011890117}, DOI={10.1073/pnas.2011890117}, abstractNote={Significance
          The neuropeptide oxytocin is an important regulator of social behavior and is widely considered to reduce anxiety-related behaviors. However, growing evidence suggests that sometimes oxytocin increases anxiety. How can the same molecule have such different effects on behavior? Here we provide evidence that oxytocin produced outside of the hypothalamus is necessary and sufficient for stress-induced social anxiety behaviors. This suggests that the diverse effects of oxytocin on anxiety-related behaviors are mediated by circuit-specific oxytocin action.}, number={42}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Duque-Wilckens, Natalia and Torres, Lisette Y. and Yokoyama, Sae and Minie, Vanessa A. and Tran, Amy and Petkova, Stela P. and Hao, Rebecca and Ramos-Maciel, Stephanie and Rios, Roberto A. and Jackson, Kenneth and et al.}, year={2020}, month={Oct}, pages={26406–26413} }
 @article{mcclain_mazzotta_maradiaga_duque-wilckens_grants_robison_christofi_moeser_gulbransen_2020, title={Histamine-dependent interactions between mast cells, glia, and neurons are altered following early-life adversity in mice and humans}, volume={319}, url={http://dx.doi.org/10.1152/ajpgi.00041.2020}, DOI={10.1152/ajpgi.00041.2020}, abstractNote={ Early-life adversity places an individual at risk for developing functional gastrointestinal disorders later in life through unknown mechanisms. Here, we show that interactions between mast cells and glia are disrupted by early-life stress in mice and that histamine is a potential mediator of mast cell-glial interactions. }, number={6}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={McClain, Jonathon L. and Mazzotta, Elvio A. and Maradiaga, Nidia and Duque-Wilckens, Natalia and Grants, Iveta and Robison, Alfred J. and Christofi, Fievos L. and Moeser, Adam J. and Gulbransen, Brian}, year={2020}, month={Dec}, pages={G655–G668} }
 @article{williams_duque-wilckens_ramos-maciel_campi_bhela_xu_jackson_chini_pesavento_trainor_2020, title={Social approach and social vigilance are differentially regulated by oxytocin receptors in the nucleus accumbens}, volume={45}, url={http://dx.doi.org/10.1038/s41386-020-0657-4}, DOI={10.1038/s41386-020-0657-4}, abstractNote={AbstractOxytocin is currently being considered as a novel therapeutic for anxiety disorders due to its ability to promote affiliative behaviors. In the nucleus accumbens (NAc) activation of oxytocin receptors (OTR) promotes social approach (time spent near an unfamiliar individual). Here, we show that stressful social experiences reduce the expression of NAc OTR mRNA, coinciding with decreases in social approach. Social stressors also increase social vigilance, characterized as orienting to an unfamiliar individual without approaching. Vigilance is a key component of behavioral inhibition, a personality trait that is a risk factor for anxiety disorders. To understand whether NAc OTR can modulate both social approach and vigilance, we use pharmacological approaches to assess the impact of activation or inhibition of NAc OTR downstream pathways on these behaviors. First, we show that in unstressed male and female California mice, inhibition of OTR by an unbiased antagonist (L-368,899) reduces social approach but does not induce social vigilance. Next, we show that infusion of Atosiban, an OTR-Gq antagonist/OTR-Gi agonist, has the same effect in unstressed females. Finally, we show that Carbetocin, a biased OTR-Gq agonist, increases social approach in stressed females while simultaneously inhibiting social vigilance. Taken together these data suggest that OTR in the NAc differentially modulate social approach and social vigilance, primarily through an OTR-Gq mechanism. Importantly, pharmacological inhibition of OTR alone is insufficient to induce vigilance in unstressed mice, suggesting that mechanisms modulating social approach may be distinct from mechanisms modulating social vigilance.}, number={9}, journal={Neuropsychopharmacology}, publisher={Springer Science and Business Media LLC}, author={Williams, Alexia V. and Duque-Wilckens, Natalia and Ramos-Maciel, Stephanie and Campi, Katharine L. and Bhela, Shanu K. and Xu, Christine K. and Jackson, Kenneth and Chini, Bice and Pesavento, Patricia A. and Trainor, Brian}, year={2020}, month={Aug}, pages={1423–1430} }
 @article{williams_manning_eagle_swift-gallant_duque-wilckens_chinnusamy_moeser_jordan_leinninger_robison_2020, title={Androgen-Dependent Excitability of Mouse Ventral Hippocampal Afferents to Nucleus Accumbens Underlies Sex-Specific Susceptibility to Stress}, volume={87}, url={http://dx.doi.org/10.1016/j.biopsych.2019.08.006}, DOI={10.1016/j.biopsych.2019.08.006}, abstractNote={Background Depression affects women nearly twice as often as men, but the neurobiological underpinnings of this discrepancy are unclear. Preclinical studies in male mice suggest that activity of ventral hippocampus (vHPC) neurons projecting to the nucleus accumbens (NAc) regulates mood-related behavioral responses to stress. We sought to characterize this circuit in both sexes and to investigate its role in potential sex differences in models of depression. Methods We used male and female adult C57BL/6J mice in the subchronic variable stress model to precipitate female-specific reduction in sucrose preference and performed gonadectomies to test the contributions of gonadal hormones to this stress response. In addition, ex vivo slice electrophysiology of transgenic Cre-inducible Rosa-eGFP-L10a mice in combination with retrograde viral tracing to identify circuits was used to test contributions of gonadal hormones to sex differences in vHPC afferents. Finally, we used an intersecting viral DREADD (designer receptor exclusively activated by designer drugs) strategy to manipulate vHPC-NAc excitability directly in awake behaving mice. Results We show a testosterone-dependent lower excitability in male versus female vHPC-NAc neurons and corresponding testosterone-dependent male resilience to reduced sucrose preference after subchronic variable stress. Importantly, we show that long-term DREADD stimulation of vHPC-NAc neurons causes decreased sucrose preference in male mice after subchronic variable stress, whereas DREADD inhibition of this circuit prevents this effect in female mice. Conclusions We demonstrate a circuit-specific sex difference in vHPC-NAc neurons that is dependent on testosterone and causes susceptibility to stress in female mice. These data provide a substantive mechanism linking gonadal hormones to cellular excitability and anhedonia—a key feature in depressive states.}, number={6}, journal={Biological Psychiatry}, publisher={Elsevier BV}, author={Williams, Elizabeth S. and Manning, Claire E. and Eagle, Andrew L. and Swift-Gallant, Ashlyn and Duque-Wilckens, Natalia and Chinnusamy, Sadhana and Moeser, Adam and Jordan, Cynthia and Leinninger, Gina and Robison, Alfred Jay}, year={2020}, month={Mar}, pages={492–501} }
 @article{mayer_crepeau_duque‐wilckens_torres_trainor_stolzenberg_2019, title={Histone deacetylase inhibitor treatment promotes spontaneous caregiving behaviour in non‐aggressive virgin male mice}, volume={31}, url={http://dx.doi.org/10.1111/jne.12734}, DOI={10.1111/jne.12734}, abstractNote={AbstractThe majority of mammalian species are uniparental, with the mother solely providing care for young conspecifics, although fathering behaviours can emerge under certain circumstances. For example, a great deal of individual variation in response to young pups has been reported in multiple inbred strains of laboratory male mice. Furthermore, sexual experience and subsequent cohabitation with a female conspecific can induce caregiving responses in otherwise indifferent, fearful or aggressive males. Thus, a highly conserved parental neural circuit is likely present in both sexes; however, the extent to which infants are capable of activating this circuit may vary. In support of this idea, fearful or indifferent responses toward pups in female mice are linked to greater immediate early gene (IEG) expression in a fear/defensive circuit involving the anterior hypothalamus compared to that in an approach/attraction circuit involving the ventral tegmental area. However, experience with infants, particularly in combination with histone deacetylase inhibitor (HDACi) treatment, can reverse this pattern of pup‐induced activation of fear/defence circuitry and promote approach behaviour. Thus, HDACi treatment may increase the transcription of primed/poised genes that play a role in the activation and selection of a maternal approach circuit in response to pup stimuli. In the present study, we investigated whether HDACi treatment would impact behavioural response selection and associated IEG expression changes in virgin male mice that are capable of ignoring, attacking or caring for pups. The results obtained indicate that systemic HDACi treatment induces spontaneous caregiving behaviour in non‐aggressive male mice and alters the pattern of pup‐induced IEG expression across a fear/defensive neural circuit.}, number={9}, journal={Journal of Neuroendocrinology}, publisher={Wiley}, author={Mayer, Heather S. and Crepeau, Marc and Duque‐Wilckens, Natalia and Torres, Lisette Y. and Trainor, Brian C. and Stolzenberg, Danielle}, year={2019}, month={Sep} }
 @article{leonzino_ponzoni_braida_gigliucci_busnelli_ceresini_duque-wilckens_nishimori_trainor_sala_et al._2019, title={Impaired approach to novelty and striatal alterations in the oxytocin receptor deficient mouse model of autism}, volume={114}, url={http://dx.doi.org/10.1016/j.yhbeh.2019.06.007}, DOI={10.1016/j.yhbeh.2019.06.007}, abstractNote={Long-standing studies established a role for the oxytocin system in social behavior, social reward, pair bonding and affiliation. Oxytocin receptors, implicated in pathological conditions affecting the social sphere such as autism spectrum disorders, can also modulate cognitive processes, an aspect generally overlooked. Here we examined the effect of acute (pharmacological) or genetic (Oxtr−/−) inactivation of oxytocin receptor-mediated signaling, in male mice, in several cognitive tests. In the novel object recognition test, both oxytocin receptor antagonist treated wild type animals and Oxtr−/− mice lacked the typical preference for novelty. Oxtr−/− mice even preferred the familiar object; moreover, their performance in the Morris water maze did not differ from wild types, suggesting that oxytocin receptor inactivation did not disrupt learning. Because the preference for novel objects could be rescued in Oxtr−/− mice with longer habituation periods, we propose that the loss of novelty preferences following Oxtr inactivation is due to altered processing of novel contextual information. Finally, we observed an increased expression of excitatory synaptic markers in the striatum of Oxtr−/− mice and a greater arborization and higher number of spines/neuron in the dorsolateral area of this structure, which drives habit formation. Our data also indicate a specific reshaping of dorsolateral striatal spines in Oxtr−/− mice after exposure to a novel environment, which might subtend their altered approach to novelty, and support previous work pointing at this structure as an important substrate for autistic behaviors.}, journal={Hormones and Behavior}, publisher={Elsevier BV}, author={Leonzino, Marianna and Ponzoni, Luisa and Braida, Daniela and Gigliucci, Valentina and Busnelli, Marta and Ceresini, Ilaria and Duque-Wilckens, Natalia and Nishimori, Katsuhiko and Trainor, Brian C. and Sala, Mariaelvina and et al.}, year={2019}, month={Aug}, pages={104543} }
 @article{steinman_duque-wilckens_trainor_2019, title={Complementary Neural Circuits for Divergent Effects of Oxytocin: Social Approach Versus Social Anxiety}, volume={85}, url={http://dx.doi.org/10.1016/j.biopsych.2018.10.008}, DOI={10.1016/j.biopsych.2018.10.008}, abstractNote={Oxytocin (OT) is widely known for promoting social interactions, but there is growing appreciation that it can sometimes induce avoidance of social contexts. The social salience hypothesis posed an innovative solution to these apparently opposing actions by proposing that OT enhances the salience of both positive and negative social interactions. The mesolimbic dopamine system was put forth as a likely system to evaluate social salience owing to its well-described role in motivation. Evidence from several sources supports the premise that OT acting within the nucleus accumbens and ventral tegmental area facilitates social reward and approach behavior. However, in aversive social contexts, additional pathways play critical roles in mediating the effects of OT. Recent data indicate that OT acts in the bed nucleus of the stria terminalis to induce avoidance of potentially dangerous social contexts. Here, we review evidence for neural circuits mediating the effects of OT in appetitive and aversive social contexts. Specifically, we propose that distinct but potentially overlapping circuits mediate OT-dependent social approach or social avoidance. We conclude that a broader and more inclusive consideration of neural circuits of social approach and avoidance is needed as the field continues to evaluate the potential of OT-based therapeutics.}, number={10}, journal={Biological Psychiatry}, publisher={Elsevier BV}, author={Steinman, Michael Q. and Duque-Wilckens, Natalia and Trainor, Brian}, year={2019}, month={May}, pages={792–801} }
 @article{duque-wilckens_steinman_busnelli_chini_yokoyama_pham_laredo_hao_perkeybile_minie_et al._2018, title={Oxytocin Receptors in the Anteromedial Bed Nucleus of the Stria Terminalis Promote Stress-Induced Social Avoidance in Female California Mice}, volume={83}, url={http://dx.doi.org/10.1016/j.biopsych.2017.08.024}, DOI={10.1016/j.biopsych.2017.08.024}, abstractNote={Background The neuropeptide oxytocin (OT) is a key regulator of social and emotional behaviors. The effects of OT are context dependent, and it has been proposed that OT increases the salience of both positive and negative social cues. Here we tested whether the bed nucleus of the stria terminalis (BNST) mediates anxiogenic effects of OT. Methods First, we studied the effects of systemic administration of an OT receptor (OTR) antagonist L-368,899 on social behavior in male and female California mice exposed to social defeat. We examined the effect of L-368,899 on G protein activation and used early growth response factor 1 immunohistochemistry to identify potential sites of OTR action. Finally, we examined the effects of L-368,899 infused in the BNST on behavior. Results A single dose of systemic L-368,899 increased social approach in stressed female mice and decreased social approach in male mice naïve to defeat. L-368,899 prevented OT activation of G proteins and did not activate G proteins in the absence of OT. Intranasal OT, which reduces social approach in female mice but not male mice, increased early growth response factor 1 immunoreactivity in the nucleus accumbens core and anteromedial BNST in female mice but not in male mice. Stressed female mice that received an infusion of L-368,899 into the anteromedial BNST but not the nucleus accumbens core increased social approach and decreased social vigilance responses. Conclusions Our results suggest that OTR activation in anteromedial BNST induces a vigilance response in which individuals avoid, yet attend to, unfamiliar social contexts. Our results suggest that OTR antagonists may have unappreciated therapeutic potential for stress-induced psychiatric disorders.}, number={3}, journal={Biological Psychiatry}, publisher={Elsevier BV}, author={Duque-Wilckens, Natalia and Steinman, Michael Q. and Busnelli, Marta and Chini, Bice and Yokoyama, Sae and Pham, Mary and Laredo, Sarah A. and Hao, Rebecca and Perkeybile, Allison M. and Minie, Vanessa A. and et al.}, year={2018}, month={Feb}, pages={203–213} }
 @article{duque-wilckens_steinman_laredo_hao_perkeybile_bales_trainor_2016, title={Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects}, volume={110}, url={http://dx.doi.org/10.1016/j.neuropharm.2016.07.018}, DOI={10.1016/j.neuropharm.2016.07.018}, abstractNote={Vasopressin V1a receptors (V1aR) are thought to contribute to the pathophysiology of psychiatric disorders such as anxiety and depression, sparking interest in V1aR as a therapeutic target. Although the global effects of V1aR have been documented, less is known about the specific neural circuits mediating these effects. Moreover, few studies have examined context-specific V1aR function in both males and females. By using the California mouse, we first studied the effects of sex and social defeat stress on V1aR binding in the forebrain. In females but not males, V1aR binding in the bed nucleus of the stria terminalis (BNST) was negatively correlated to social interaction behavior. In females stress also increased V1aR binding in the nucleus accumbens (NAc). Infusions of V1aR antagonist in to the medioventral BNST (BNSTmv) had anxiogenic effects only in animals naïve to defeat. For males, inhibition of V1aR in BNSTmv had anxiogenic effects in social and nonsocial contexts, but for females, anxiogenic effects were limited to social contexts. In stressed females, inhibition of V1aR in the NAc shell had no effect on social interaction behavior, but had an anxiogenic effect in an open field test. These data suggest that V1aR in BNSTmv have anxiolytic and prosocial effects in males, and that in females, prosocial and anxiolytic effects of V1aR appear to be mediated independently by receptors in the BNSTmv and NAc shell, respectively. These findings suggest that males have more overlap in neural circuits modulating anxiety in social and nonsocial contexts than females.}, journal={Neuropharmacology}, publisher={Elsevier BV}, author={Duque-Wilckens, Natalia and Steinman, Michael Q. and Laredo, Sarah A. and Hao, Rebecca and Perkeybile, Allison M. and Bales, Karen L. and Trainor, Brian C.}, year={2016}, month={Nov}, pages={59–68} }
 @article{steinman_duque-wilckens_greenberg_hao_campi_laredo_laman-maharg_manning_doig_lopez_et al._2016, title={Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin}, volume={80}, url={http://dx.doi.org/10.1016/j.biopsych.2015.10.007}, DOI={10.1016/j.biopsych.2015.10.007}, abstractNote={<h2>Abstract</h2><h3>Background</h3> Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice. <h3>Methods</h3> We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (<i>n</i> = 6–9) and 2 weeks (<i>n</i> = 6–9) and 10 weeks (<i>n</i> = 4–5) later. We quantified <i>Oxt</i> messenger RNA with quantitative polymerase chain reaction (<i>n</i> = 5–9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (<i>n</i> = 8–14). <h3>Results</h3> Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased <i>Oxt</i> messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test. <h3>Conclusions</h3> Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress.}, number={5}, journal={Biological Psychiatry}, publisher={Elsevier BV}, author={Steinman, Michael Q. and Duque-Wilckens, Natalia and Greenberg, Gian D. and Hao, Rebecca and Campi, Katharine L. and Laredo, Sarah A. and Laman-Maharg, Abigail and Manning, Claire E. and Doig, Ian E. and Lopez, Eduardo M. and et al.}, year={2016}, month={Sep}, pages={406–414} }