Aggressive behavior is an adaptive trait present across all taxa. However, the neuroendocrine mechanisms regulating it, particularly in fish, are not well understood. Oxytocin (OXT) and arginine vasotocin (VT) are known...Aggressive behavior is an adaptive trait present across all taxa. However, the neuroendocrine mechanisms regulating it, particularly in fish, are not well understood. Oxytocin (OXT) and arginine vasotocin (VT) are known modulators of aggression, but their actions remain controversial. This study tested the possible modulation of endocrine and behavioral responses to an aggression challenge by these nonapeptides in Siamese fighting fish, Betta splendens, a species known for its intrinsic aggressiveness. Male B. splendens were injected with different dosages of either Manning compound or L-368,899, VT and OXT receptor antagonists respectively, and were exposed to a mirror challenge for 30 min. While all fish displayed high levels of aggression toward their mirror image, no differences were observed between control-injected and treatment fish. However, blocking VT inhibited the post-fight increase in plasma levels of the androgen 11-ketotestosterone (KT). To further investigate this result, testis tissue from males was incubated with and without VT and Manning compound, and KT levels were measured after 180 min. Results showed a direct effect of VT on in vitro KT secretion, indicating the presence of VT receptors in the testes of this species. Overall, the study does not support a modulatory role of VT or OXT in aggressive behavior, although VT might be implicated in the regulation of peripheral androgen response to aggression in B. splendens.
Millions of people take hormonal contraceptives (HCs), often starting during adolescence when ovarian hormones influence brain and behavioral maturation. However, there is a fundamental lack of information about the neur...Millions of people take hormonal contraceptives (HCs), often starting during adolescence when ovarian hormones influence brain and behavioral maturation. However, there is a fundamental lack of information about the neurobehavioral consequences of hormonal alterations via adolescent HC use. To begin addressing this gap, we validated a rodent model of adolescent HC administration and characterized its impact on endocrine, transcriptional, and behavioral endpoints. Cohorts of intact post-pubertal female Sprague-Dawley rats received daily subcutaneous injections of either vehicle or HC [10 μg ethinyl estradiol (EE) + 20 μg levonorgestrel (LNG)] for the duration of adolescence from postnatal day (PND) 35 to PND56. Blood and brain tissue was collected at PND57. Other cohorts received daily injections of vehicle or HC from PND35 until behavioral assays were completed on PND57-64. HC treatment was effective, as vaginal lavage indicated disrupted estrous cycling and ELISA indicated suppressed serum luteinizing hormone in HC-treated rats. Liquid chromatography-mass spectrometry analysis showed EE and LNG in serum and brain as well as diminished serum and brain levels of allopregnanolone and testosterone in HC-treated rats. NanoString nCounter analysis indicated that adolescent HC administration impacted expression of genes related to synapses, white matter, neuroimmune, monoamine, and hormone signaling in the hypothalamus and medial prefrontal cortex. While no effects of HCs were seen on sociability in the social preference test or stress coping behavior in the forced swim test, adolescent HC administration diminished risk-assessment behaviors in the novelty-induced hypophagia paradigm and altered anxiety-like behavior in the open field test and elevated plus maze. Overall, these data suggest that exposure to contraceptive hormones during the critical developmental period of adolescence may shape the brain and behavior.
Oxytocin receptor (OXTR) activity in the nucleus accumbens (NAc) is critical for pair bonding in prairie voles. Oxtr knockdown or pharmacological blockade in this region prevents mating-induced partner preferences, while...Oxytocin receptor (OXTR) activity in the nucleus accumbens (NAc) is critical for pair bonding in prairie voles. Oxtr knockdown or pharmacological blockade in this region prevents mating-induced partner preferences, while overexpression facilitates bonding. However, no prior work has selectively interrogated or manipulated Oxtr-expressing neurons during dynamic bonding behaviors. We have developed an Oxtr-P2A-Cre prairie vole line that enables direct access to specific Oxtr neural populations. We utilized Oxtr-P2A-Cre prairie voles to express inhibitory DREADDs selectively in OXTR-expressing NAc neurons. Inhibiting NAc OXTR cells during initial cohabitation did not affect subsequent partner preference formation; however, inhibition during partner preference testing increased partner-directed huddling behavior, revealing a complex role for these neurons in social interactions. Using a viral tracing approach, we found that NAc OXTR-expressing neurons receive prominent inputs from the medial prefrontal cortex, hippocampus, thalamus, and hypothalamus, while projecting strongly to the ventral pallidum, ventral tegmental area, and lateral hypothalamus. Our cell-type-specific manipulation reveals how oxytocin receptor signaling in the NAc may modulate emotional state and facilitate the complex social behaviors underlying monogamous pair bonding. This Cre-recombinase approach demonstrates the utility of cell-type-specific targeting for elucidating oxytocin neural circuit mechanisms regulating emotional and social behavior in prairie voles.
Urban wildlife must cope with diverse challenges and stressors, including human presence. However, in addition to being a disturbance, humans can provide energy-rich food and protection from predators. We evaluated the i...Urban wildlife must cope with diverse challenges and stressors, including human presence. However, in addition to being a disturbance, humans can provide energy-rich food and protection from predators. We evaluated the impact of human presence on red-winged starlings (Onychognathus morio) in a highly urbanised environment using faecal glucocorticoid metabolite (fGCM) concentrations as a stress-related biomarker. We performed an adrenocorticotropic hormone (ACTH) challenge to validate a non-invasive method for quantifying glucocorticoids in red-winged starlings. Using this method, we quantified fGCMs in excreta collected from free-living starlings during weekdays (high human presence) and weekends (low human presence) to determine the birds' responses to fluctuating human numbers. Following the ACTH challenge, starlings' circulating glucocorticoid (GC) concentrations increased by 127 % within 30 min and the corresponding fGCM concentrations increased within 1 h of injection. Of the four enzyme immunoassays (EIA) tested, an 11-oxoaetiocholanolone EIA, performed best, detecting a 310 % increase in fGCM concentrations post-ACTH challenge and suggested a 1-h lag between injection and peak fGCM excretion in this species. Human foot-traffic was significantly higher on weekdays compared to weekends, yet free-living red-winged starlings showed overall 30.4 % lower fGCM concentrations on weekdays compared to weekends. Red-winged starlings consume a higher proportion of anthropogenic food on weekdays than weekends and we cannot rule out the possibility that diet-related alteration in gut passage time affect fGCM concentrations. However, the correlation between fGCMs and human foot traffic may also suggest urban red-winged starlings benefit from human presence. Our results raise the possibility that, under certain conditions, the benefits associated with human presence outweigh potential negative effects associated with human activity, at least during the non-breeding season.
Aromatase (Aro+) neurons located in the Bed Nucleus of the Stria Terminalis (BNST) are crucial for the display of both sexual behavior and territorial aggression in naive male mice. The postero-dorsal part of the Medial...Aromatase (Aro+) neurons located in the Bed Nucleus of the Stria Terminalis (BNST) are crucial for the display of both sexual behavior and territorial aggression in naive male mice. The postero-dorsal part of the Medial Amygdala (MeApd) also contains Aro + neurons that are required for territorial aggression, but these neurons seem dispensable for the display of sexual behavior in naive animals. However, little is known about how Aro + neuron circuitry is influenced by social experience. Using a combination of chemogenetics, activity mapping and retrograde viral tracing, we show that social experience modulates Aro + neurons during sexual behavior and territorial aggression. Chemogenetic inhibition of BNST Aro + neurons in socially experienced male mice revealed that these neurons are required for territorial aggression, but not for sexual behavior. Behavior testing in experienced animals showed a specific increase in activation in the vomeronasal organ (VNO) and the Medial Amygdala (MeA) after sexual behavior but not territorial aggression, assessed by Egr1 expression. We also observed an increase of Egr1 cells in the medial Preoptic Area (mPOA), a brain region implicated in the display of sexual behavior. Combined retrograde viral tracing and Egr1 immunodetection showed that a subset of the activated cells in the MeA are Aro + neurons projecting to the mPOA. These results highlight that social experience induces a differential neural activity in the circuitry controlling sexual behavior and aggression, which include MeA Aro + neurons projecting to the mPOA.
Based on claims that changes in women's hormone levels influence their mating psychology, the Congruency Hypothesis proposes that women in relationships who change their hormonal contraceptive use after meeting their par...Based on claims that changes in women's hormone levels influence their mating psychology, the Congruency Hypothesis proposes that women in relationships who change their hormonal contraceptive use after meeting their partner will report lower sexual satisfaction with their partner than women who do not change their oral contraceptive use. However, findings from studies testing this hypothesis have reported mixed results. Consequently, we conducted a meta-analysis of published studies on this topic. For the thirteen effects sizes from studies using between-subjects designs, the pooled correlation between congruency and sexual satisfaction was not statistically significant (r = 0.04, p = .091) and a Robust Bayesian meta-analysis found that the null hypothesis was moderately favoured over the Congruency Hypothesis (BF = 0.123, i.e., BF = 8.13, r = 0.003). For the four effect sizes from studies using within-subjects designs, the pooled correlation between congruency and sexual satisfaction was statistically significant (r = 0.18, p = .001) and a Robust Bayesian meta-analysis found weak evidence in favour of the Congruency Hypothesis (BF = 1.55, r = 0.09). Although the effect of congruency on sexual satisfaction may be statistically significant in some analyses, across all analyses, results indicated that the magnitude of the congruency effect was small. Thus, we suggest that it is unlikely that changes in oral contraceptive use have a substantial (i.e., large) effect on women's sexual satisfaction on average. Still, some women might experience congruency effects and the overall evidence remains uncertain. More work, ideally in the form of randomized controlled trials, is needed to find a definite answer for research questions relying on the Congruency Hypothesis.
In both humans and rodents, maternal care is disturbed by exposure to environmental adversity, including low resource conditions (i.e., poverty, scarcity). Maternal adversity is associated with compromised quality of mot...In both humans and rodents, maternal care is disturbed by exposure to environmental adversity, including low resource conditions (i.e., poverty, scarcity). Maternal adversity is associated with compromised quality of mother-infant attachment and increased adverse caregiving patterns such as abuse, maltreatment and/or neglect, which disrupt behavioral development in the female offspring. Importantly, maternal behavior is thought to be an intergenerational behavior, meaning that the quality of maternal care a female experiences during early life is thought to influence the quality of care she will display towards her own offspring when she becomes a mother. Here, we tested this idea by employing a rodent model of postpartum environmental adversity based on creating an impoverished nesting environment during postpartum days (PD) 2-9, which disrupts mother-infant interactions and is thought to upregulate hypothalamic-pituitary-adrenal (HPA)-axis function in the pups. We examined the impact of this form of early life adversity on pup stress hormone (i.e., corticosterone- CORT) levels by collecting trunk blood and later life maternal behavior by conducting maternal behavior observations and maternal motivation tests (e.g., T-Maze, pup retrieval, pup-associated conditioned place preference) in the first filial (F1) generation. We report no impact of early life scarcity-adversity/adverse caregiving on pup CORT levels or later life naturalistic or motivated maternal behaviors. In sum, we show that female rat pups who experienced adverse caregiving during early life showed resilience towards developing negative caregiving patterns, as they did not perpetuate the same aberrant maternal behavior that they received from their mothers.
Spatial memory declines with age, and this decline is associated with decreased testosterone levels. However, the specific role of the androgen receptor in spatial memory performance in both young and aged rats remains l...Spatial memory declines with age, and this decline is associated with decreased testosterone levels. However, the specific role of the androgen receptor in spatial memory performance in both young and aged rats remains largely unexplored. Our study aimed to investigate the effects of chronic androgen receptor blockade on spatial memory performance in young and aged male rats. Young (3 months old) and aged (21 months old) Wistar rats were assigned to one of three experimental groups: control, vehicle-, or flutamide-treated (10 mg/kg SC for 14 days). Spatial memory was evaluated using the Barnes maze (Days 8-14 of flutamide administration). The phases of spatial memory acquisition (4 daily trials/4 days) and retention (1 trial/day, 3 days after acquisition) were evaluated. The results indicated that older animals took longer to find the goal, traveled greater distances, and moved more slowly than their younger counterparts in the Barnes maze, regardless of treatment. During the acquisition phase, flutamide administration delayed learning in both young and aged animals. Specifically, flutamide-treated animals exhibited delayed learning during the assessment of overnight forgetting (trial 1 on each day of the acquisition phase). During the retention phase, an age-related effect was observed in the flutamide-treated groups. These findings suggest that androgen receptor blockade induces cognitive deficits in both young and aged male rats, supporting the modulatory role of endogenous androgens in memory function.
Research conducted over the last several decades implicates ovarian estrogens as important modulators of hippocampal function. More recently however, the importance of estrogens synthesized in the brain de novo for hippo...Research conducted over the last several decades implicates ovarian estrogens as important modulators of hippocampal function. More recently however, the importance of estrogens synthesized in the brain de novo for hippocampal function has been recognized. These brain-derived neuroestrogens act in the hippocampus to regulate dendritic spine dynamics and synaptic plasticity as well as hippocampus-dependent memory. The current report provides an overview of research conducted in model systems elucidating the actions of neuroestrogens in the hippocampus and the subsequent consequences for cognition. We highlight the relationship between ovarian estrogens and brain-derived estrogens and discuss implications for female cognitive aging of the putative decline in hippocampal levels of neuroestrogens following loss of ovarian function. Finally, we propose a model of menopause in which a short-term period of midlife estradiol treatment changes the trajectory of hippocampal neuroestrogen production long-term, resulting in sustained interactions of neuroestrogens, insulin-like growth factor-1, and estrogen receptor signaling in the hippocampus, interactions that support successful brain and cognitive aging.
Throughout history, women have faced numerous threats during pregnancy, some of which can be mitigated by a strong social network. Consequently, women may demonstrate behavioral changes that bolster their social support...Throughout history, women have faced numerous threats during pregnancy, some of which can be mitigated by a strong social network. Consequently, women may demonstrate behavioral changes that bolster their social support network during pregnancy and in the luteal phase of the menstrual cycle. We examined whether women's explicit desire to affiliate varied across menstrual cycle phases and was associated with within-woman fluctuations in progesterone and estradiol. Supporting our hypotheses, women demonstrated increased desire to affiliate in the luteal phase of the cycle, and this increase was especially pronounced for affiliation with close others. Moreover, desire to affiliate indeed tended to be positively associated with within-woman fluctuations in progesterone, although the negative association between women's desire to affiliate and within-woman fluctuations in estradiol was more robust across analyses. This research links women's explicit desire for social connection to endocrinological processes across the menstrual cycle and, more broadly, to recurrent challenges faced by pregnant women throughout evolutionary history.
Postnatal stress can affect behavior and physiology in vertebrates, but long-term effects of early-life stress experience are not well understood, especially in wild species. Glucocorticoids, steroid hormones that mediat...Postnatal stress can affect behavior and physiology in vertebrates, but long-term effects of early-life stress experience are not well understood, especially in wild species. Glucocorticoids, steroid hormones that mediate a suite of physiological and behavioral traits in response to a changing environment, might play an important role in programming long-term responses. We examined the effects of early-life exposure to corticosterone, the primary avian glucocorticoid, on neophobic and competitive behaviors in the house sparrow (Passer domesticus). We manipulated circulating corticosterone levels in wild, free-living nestlings, then measured behavior at the juvenile and adult stages in captivity. Birds were independently tested on their response to a novel object (i.e., neophobia) and tested in their nest group on their response to a limited food source (i.e., competitive behaviors). We had alternate predictions: (1) corticosterone-treated birds would exhibit fewer neophobic behaviors and more competitive behaviors than controls if early-life corticosterone exposure adaptively prepares animals for high-stress environments; or (2) corticosterone-treated birds would be more neophobic and less competitive compared to controls if high early-life corticosterone exposure outpaces the organism's capacity to regulate stability. Additionally, we predicted that postnatal corticosterone exposure might affect juvenile behavior more than adult behavior if responses can be modulated by individual experiences over time. We found that early-life corticosterone exposure largely did not predict neophobic behaviors in response to a novel object and environment but did predict competitive behaviors in juveniles. Corticosterone-treated juvenile males tended to be less competitive and displaced more frequently than control juvenile males, whereas corticosterone-treated juvenile females tended to be more competitive than control juvenile females; however, these patterns were no longer present by adulthood. We conclude that early-life stress might have sex-specific effects in a bird's competitive ability in their first year of life, which could impact survival in populations facing novel stressors.
Study design and experimental tools are crucial for good quality science, and an essential part of it is the choice of control groups to best test the hypothesis. Two of the standard control groups in physiological and p...Study design and experimental tools are crucial for good quality science, and an essential part of it is the choice of control groups to best test the hypothesis. Two of the standard control groups in physiological and pharmacological research are needle pricking without substance injection (Sham) and/or vehicle injection (Saline). However, both needle pricking and saline injection can act as stressors, potentially influencing the analyzed outcome. This raises the question of whether the dependent variable remains unaffected by the stress induced by these procedures. Despite the significance of this issue, very few studies have investigated the behavioral effects of a single intraperitoneal (I.P.) Sham and/or single I.P. Saline injection in mice, and those that have used mostly adult males. In this study, we investigated if a single I.P. Sham and/or I.P. Saline injection affects female and male prepubertal (4-weeks-old) mice behavior. After Sham or Saline injection, we examined exploratory/motor behavior (open field test - OFT), anxiety-like behavior (elevated plus-maze - EPM), and behavioral despair/depressive-like behavior (forced swimming test - FST). We observed that both Sham prepubertal females and males showed behavioral alterations in OFT and EPM, and Saline males showed behavioral alterations in OFT and FST. On the other hand, prepubertal Saline females showed an increase in exploratory behavior, risk assessment/anxiety-like behavior, and behavioral despair/depressive-like behavior. Thus, our findings indicate that control procedures commonly used in physiological and pharmacological experimental designs affect the behavior of prepubescent mice, with more pronounced effects in females than in males. This study suggests considering Naïve animals together with Sham and/or Vehicle for a better and more honest interpretation of the data.
Prosocial behaviors, including empathetic consoling toward others, contribute to maintaining social groups and social connections between individuals in many mammalian species, including monogamous prairie voles (Microtu...Prosocial behaviors, including empathetic consoling toward others, contribute to maintaining social groups and social connections between individuals in many mammalian species, including monogamous prairie voles (Microtus ochrogaster). Prairie voles display consolation toward distressed partners by increasing allogrooming behavior toward the partner. A previous pharmacological study showed that oxytocin signaling contributes to consolation in male prairie voles, although possible sex differences in the regulation of consoling have not been explored. Here, we demonstrate that male, but not female, oxytocin receptor knockout (Oxtr) prairie voles display disrupted consoling behavior toward distressed opposite sex partners who spend 24 h with their partners to form a pair bond. Notably, both male and female Oxtr prairie voles showed normal partner preference following 24 h of cohabitation. Autoradiography for the vasopressin 1a receptor (AVPR1A) reveals no differences between genotypes in AVPR1A levels in the lateral septum, ventral pallidum, laterodorsal thalamic nucleus, and central amygdala, suggesting that the lack of OXTR does not lead to compensation via AVPR1A system at the receptor expression level in these selected brain regions. These findings demonstrate that OXTR modulates consolation in a sex-specific manner in prairie voles, while the lack of OXTR does not influence pair bonding.
This short essay is based on the presentation I gave at the meeting of the Society of Behavioral Neuroendocrinology held in Tours, France in June 2023 when I received the Lehrman award for career achievement. I conducted...This short essay is based on the presentation I gave at the meeting of the Society of Behavioral Neuroendocrinology held in Tours, France in June 2023 when I received the Lehrman award for career achievement. I conducted my PhD at the Institute of Animal Behavior that was founded by Lehrman at Rutgers University. Although I never met Lehrman I was mentored by several scientists who had worked with him. I therefore decided to organize my essay about the Lehrman award around the enduring legacy of Lehrman's work as it influenced my career. Four aspects of the scientific legacy of Daniel Lehrman are distinguished and I discuss how these insights affected my own research program. A concise summary of the research I conducted in collaboration with PhD students and postdocs that relates to these topics is then presented. This research that involves several avian species includes studies of how behavior can influence the endocrine physiology and behavior of receivers of a particular signal. The cloning of the gonadotropin-releasing hormone (GnRH) gene in songbirds and analysis of the environmental factors influencing its expression demonstrated how the GnRH neuronal system is a key link between the perception of behavior and changes in endocrine physiology. Finally, there is a review of studies of the experimental analysis of the brain sites where testosterone acts to control the motivation to sing and the quality of song in songbirds that follow directly in the Lehrman line of work on how steroids regulate avian reproductive behaviors.
Territorial competition can stimulate secretion of testosterone (T), which is thought to act on neural circuits of aggression to promote further aggression. Here, we test the hypothesis that competition modulates sex ste...Territorial competition can stimulate secretion of testosterone (T), which is thought to act on neural circuits of aggression to promote further aggression. Here, we test the hypothesis that competition modulates sex steroid sensitivity and conversion in the brain, focused on the female tree swallow (Tachycineta bicolor). In this bird species, exogenous T enhances female aggression, but social competition for limited nesting territories does not stimulate systemic T elevation. We exposed free-living females to simulated territorial intrusions and sampled five regions of the vertebrate social behavior network (SBN). Using quantitative PCR, we measured mRNA abundance of: androgen receptor, 5-alpha reductase, estrogen receptor alpha, and aromatase. Using standard analyses, we found essentially no treatment effect on mRNA abundance in any one brain area; however, network analyses revealed marked socially-induced changes in gene co-expression across the SBN. After a territorial challenge, gene expression was more positively correlated with T, and genes specific to the androgen-signaling pathway were also more positively correlated with one another. The challenged brain also exhibited stronger negative correlations among genes in the nucleus taeniae, but stronger positive correlations between the lateral septum and bed nucleus of the stria terminalis. Together, these findings suggest that, in response to female-female territorial challenges, T acts on androgen-mediated circuits of aggression, with some divergence in gene regulation in the nucleus taeniae. The post-transcriptional consequences of these shifts require more research, but their existence underscores insights to be gained from analyzing the neuroendocrine properties of the SBN using network-level perspectives.
Ovarian hormones, particularly estradiol, play an important role in the regulation of metabolic function including in food intake, thermogenesis, activity, fat distribution, and overall weight management. While it is kno...Ovarian hormones, particularly estradiol, play an important role in the regulation of metabolic function including in food intake, thermogenesis, activity, fat distribution, and overall weight management. While it is known that weight and food intake follow cyclical patterns across the rodent estrous cycle, the majority of metabolic studies still focus on ovariectomized rodent models and estrogen replacement. Here we provide a comprehensive metabolic profiling of female mice under different ovarian hormone states, from having naturally-cycling ovarian hormone levels to complete ovarian hormone depletion and "estrous cycle-like" estrogen replacement (0.2 or 1 μg estradiol benzoate every 4 days). Every domain of metabolic function that we examined including activity levels, food intake, and body composition was affected by ovariectomy and contributed to >30 % weight gain and nearly two-fold increase in fat mass in ovarian hormone-depleted mice over the 12-week period. By combining physiological and hormone replacement paradigms, we show that cyclical estrogen levels are necessary and sufficient to maintain optimal body weight and fat mass. We show that the hypothalamic expression of genes encoding estrogen receptor alpha (Esr1) and neuropeptides involved in feeding behavior (Agrp, Pomc) changes across the cycle and with ovariectomy, and is partially "rescued" by cyclical estrogen treatment. The drastic fat mass changes following ovariectomy are accompanied by changes in adipose tissue gene expression, including a decreased responsiveness to estrogens due to Esr1 down-regulation. Our study highlights the importance of understanding the dynamic regulation of metabolic function by ovarian hormones and calls for more naturalistic and higher-resolution approaches to studying the molecular basis of ovarian hormone action.
Our understanding of the endocrine regulation of migration comes primarily from studies of obligate migrants, which make predictable seasonal movements. Less well studied are facultative migrations, which are more variab...Our understanding of the endocrine regulation of migration comes primarily from studies of obligate migrants, which make predictable seasonal movements. Less well studied are facultative migrations, which are more variable in timing, distance, and direction. In obligate migrants, an increase in circulating testosterone appears to be important in stimulating the transition to a spring migratory state, though the mechanism by which testosterone exerts these effects remains poorly understood. The pine siskin (Spinus pinus) is a songbird that exhibits spring nomadism, a form of facultative migration. Using captive male pine siskins, we first tested the hypotheses that circulating androgens stimulate (i) physiological preparation and (ii) the expression of behavioral readiness for nomadic migration. We found that when birds were given subcutaneous implants containing exogenous testosterone, they exhibited greater nocturnal migratory restlessness, but generally not greater physiological preparation, compared to control birds. Further, when we inhibited the effects of testosterone by giving subcutaneous implants of androgen receptor antagonist and aromatase inhibitor these birds showed less nocturnal migratory restlessness compared to control birds, though the groups did not differ in physiological preparations. We then tested whether the effects of testosterone are mediated by activation of androgen receptors or estrogen receptors by giving androgen receptor antagonist and aromatase inhibitor separately. This manipulation provided some evidence that the effects of testosterone on migratory restlessness occur via activation of androgen receptors and suggested a role for androgen receptor activation in physiological preparations. Overall, the results indicate a role for testosterone in stimulating spring nomadic migratory behavior in male pine siskins.
Endocrine-disrupting chemicals (EDCs) are environmental toxicants that disrupt hormonal and neurodevelopmental processes. Among these chemicals, polychlorinated biphenyls (PCBs) are particularly concerning due to their r...Endocrine-disrupting chemicals (EDCs) are environmental toxicants that disrupt hormonal and neurodevelopmental processes. Among these chemicals, polychlorinated biphenyls (PCBs) are particularly concerning due to their resistance to biodegradation and tendency to bioaccumulate. PCBs affect neurodevelopmental function and disrupt the brain's dopamine (DA) system, which is crucial for attentional, affective, and reward processing. These disruptions may contribute to the rising prevalence of DA-mediated neuropsychiatric disorders such as ADHD, depression, and substance use disorders. Notably, these behaviors are sexually dimorphic in part due to differences in sex hormones and their receptors, which are targets of estrogenic PCBs. Therefore, this study determined effects of early life PCB exposure on behaviors and neurochemistry related to potential disruption of dopaminergic signaling. Male and female Sprague Dawley rats were exposed to the PCB mixture Aroclor 1221 (A1221) or vehicle perinatally and then underwent a series of behavioral tests in adulthood, including the sucrose preference test to measure anhedonia, conditioned orienting to assess incentive-motivational phenotype, and attentional set-shifting to evaluate cognitive flexibility and response latency. Following these tests, rats were euthanized, and serum estradiol (E2), DA cells in the midbrain ventral tegmental area (VTA) and substantia nigra (SN), and gene expression from those combined midbrain nuclei were measured. Female rats exposed perinatally to A1221 exhibited decreased sucrose preference, and both male and female A1221 rats had reduced response latency in the attentional set-shifting task compared to vehicle counterparts. Conditioned orienting and serum estradiol (E2)were not affected in either sex; however, A1221-exposed rats of both sexes displayed higher TH+ cell numbers in the VTA and increased expression of dopamine receptor 1 (Drd1) in the combined midbrain nuclei. Additionally, E2 uniquely predicted behavioral outcomes and VTA DAergic cell numbers in A1221-exposed female rats, whereas DA signaling genes were predictive of behavioral outcomes in males. These data highlight sex-specific effects of A1221 on neuromolecular and behavioral phenotypes.
The role that estrogens play in the dynamic modulation of social behaviors related to reproduction has been well established, yet whether they can acutely modulate social responses outside of reproductive contexts remain...The role that estrogens play in the dynamic modulation of social behaviors related to reproduction has been well established, yet whether they can acutely modulate social responses outside of reproductive contexts remains less clear. Further, while estrogens typically promote aggressive responses in competitive contexts, especially in territorial species, it is possible they enhance non-sexual, prosocial interactions in other contexts, especially in species that live in groups. We therefore tested the acute effects of two doses of estradiol (E2) and of an aromatase inhibitor, Fadrozole, on social approach/preference responses for same-sex shoals in male and female zebrafish, as well as the effects of an agonist for the membrane G-protein coupled estrogen receptor (GPER). Estradiol, added to the water at a dose of 10-6 M, was able to significantly increase approach/preference responses in both sexes in multiple experiments in <1 h, whereas Fadrozole inhibited social approach responses 1 h and 17 h after exposure in females, but not in males. A GPER agonist did not enhance social preference responses like E2 did. Neither the effects of E2 nor FAD were paralleled by influences on measures of stress/anxiety, indicating E2 rapidly increases tendencies to approach and maintain proximity to groups in this highly social species through direct actions on social brain circuits.
Aggressive behavior is ubiquitous across many contexts, including defense of territories, mates, and offspring. For decades, researchers have detailed the effect of aggressive behavior on physiology, but our understandin...Aggressive behavior is ubiquitous across many contexts, including defense of territories, mates, and offspring. For decades, researchers have detailed the effect of aggressive behavior on physiology, but our understanding of these mechanisms in females lags behind that of males, despite the fact that female aggression is widespread, particularly in the context of maternal defense of eggs or offspring (i.e., maternal aggression). Here, we measured effects of a social challenge on brain gene expression in free-living incubating females. We hypothesized that the social challenge would generate at least one of three transcriptomic effects: (1) sensitizing the brain to otherwise low levels of sex steroids, (2) changing other neuroendocrine signaling pathways associated with social behavior (e.g., dopamine), or (3) broad shifts related to metabolism or immune function. We tested these hypotheses in incubating female tree swallows (Tachycineta bicolor), exposing 10 females to a 30-min simulated territorial intrusion, which elicited maternal aggression. After this challenge, we measured neural gene expression via RNA-seq and compared gene expression to 10 unchallenged controls. We saw no global treatment effect on gene expression. However, within the experimental group, more maternal aggression was correlated with upregulation of genes associated with immune activation and downregulation of genes associated with synaptic plasticity. Though more research is needed to understand the downstream effects of these transcriptional differences, our findings generate key questions about how the brain responds to social challenges across different contexts.