Hormones And Behavior[JOURNAL]
Sun
200 papers
Do combined oral contraceptives have long-term effects? Little evidence of an enduring effect on cognitive function in former users.
Hampson E
Horm Behav · 2025 Aug · PMID 40749444 · Publisher ↗
The use of combined oral contraceptives (COCs) is associated with subtle differences in brain activity and in certain cognitive, perceptual, or affective processes among current COC users compared with non-users. Whether...
The use of combined oral contraceptives (COCs) is associated with subtle differences in brain activity and in certain cognitive, perceptual, or affective processes among current COC users compared with non-users. Whether any differences persist after the COCs are discontinued is essentially unknown. In a retrospective analysis of a cognitive dataset from healthy adults (N = 221, M = 23.78 yrs), we asked whether any residual effects of COC use could be identified in former users (who had discontinued their COCs ∼30 mo prior) on standardized tests of verbal fluency and visuospatial function. A detailed reproductive history was available, including specifics of any past COC use. Cognition was evaluated during the early follicular phase of the menstrual cycle when the ovaries are quiescent and hormone production is lowest. Based on their reproductive history, participants were classified as former users of COCs (N = 86, mean duration of COC use = 29.89 mo), never-users (N = 106, no past use of hormonal contraceptives), or current users (N = 29, currently using a COC, mean duration of COC use = 29.72 mo). All COCs contained either levonorgestrel or a progestin from the norethindrone family, and 30-35 μg/day of ethinyl estradiol. Analysis of covariance (ANCOVA) contrasting cognitive performance in the 3 groups showed that despite the use of androgenic progestins and an estradiol dose that was relatively high, there was no evidence of a difference between former-users and never-users on any of the cognitive tests. Current users scored lower than former or never users on a conventional visuospatial task (Space Relations). Partial correlations controlling for age, estimated IQ, and pregnancy history revealed that duration of past COC use in former users was significantly associated with verbal fluency on one of two phonemic fluency tasks administered. A longer duration of COC use was associated with poorer word generation ability. This dataset produced little evidence of any enduring effects of COC use, however a duration-dependent association between former COC use and verbal fluency reinforces a similar trend reported previously among current users.
Are women's sexual preferences for men's facial hair associated with their testosterone during the menstrual cycle?
Dixson BJW, Lee AJ, Jasienska G … +1 more , Marcinkowska UM
Horm Behav · 2025 Aug · PMID 40743807 · Publisher ↗
The ovulatory shift hypothesis proposes that women's mate preferences for androgen-dependent secondary sexual traits in men are most pronounced during the ovulatory phase of the menstrual cycle. Using an appropriately po...
The ovulatory shift hypothesis proposes that women's mate preferences for androgen-dependent secondary sexual traits in men are most pronounced during the ovulatory phase of the menstrual cycle. Using an appropriately powered within-subjects design, we provide the first test of whether women's sexual preferences for male facial hair, which is reliably associated with male sexual maturity and masculinity, peak during the ovulatory phase among women with higher salivary testosterone. Sixty-five heterosexual women completed the study, which included a two-alternative forced choice preference test wherein participants selected the face they found most sexually attractive from pairs of composite images of the same men when fully bearded and when clean-shaven. The task was completed among the same participants during the follicular, ovulatory (validated by the surge in luteinizing hormone) and luteal phases. Participants also provided saliva samples for subsequent assaying of testosterone. We ran two models, both of which showed strong preferences among women for bearded over clean-shaven composite faces. In our first model, women's preferences for bearded faces were negatively associated with their salivary testosterone levels. In our second model, in which we included women's menstrual cycle phase, this negative association appeared to be driven by preferences among women in the ovulatory and follicular phases. However, the main effect of cycle phase and the interaction between testosterone and cycle phase were not statistically significant. Although further replication is required to confirm our findings, for the present we conclude that women's preferences for men's beardedness may not be related to changes in their salivary testosterone over the menstrual cycle in ways that support the ovulatory shift hypothesis.
Multiparity alters expression of corticotropin releasing factor receptor 1 and co-expression with oxytocin neurons in mice.
Parra KE, Lafrican JJ, Rybka KA … +7 more , Neuwirth AE, Chait LS, Della Posta AV, Greenwood AL, Zuloaga KL, Justice NJ, Zuloaga DG
Horm Behav · 2025 Aug · PMID 40738027 · Full text
Corticotropin releasing factor (CRF) signaling through its primary receptor (CRFR1) regulates various stress-related behaviors and neuroendocrine responses. CRFR1 is also a key regulator of stress-related behavior change...
Corticotropin releasing factor (CRF) signaling through its primary receptor (CRFR1) regulates various stress-related behaviors and neuroendocrine responses. CRFR1 is also a key regulator of stress-related behavior changes during the postpartum period in rodents. Previous studies indicate dynamic changes in CRFR1 in various brain regions during the first postpartum period including an emergence of CRFR1 expression in hypothalamic oxytocin neurons. We sought to determine how these changes in CRFR1 and CRFR1/oxytocin co-expression might be altered with repeated breeding cycles and whether these neural adaptations coincide with changes in maternal behaviors that are reported to occur in rodent dams with greater maternal experience. CRFR1-GFP reporter mice were bred to produce 1 (primiparous) or 3 (multiparous) litters and were assessed for pup retrieval in unstressed and stressed (male intruder) conditions. Brains of nulliparous, primiparous, and multiparous mice were collected to assess CRFR1-GFP and co-expression of CRFR1 with oxytocin. No statistically significant changes in pup retrieval were found between primiparous and multiparous mice although both groups showed a greater latency to hover over pups following male intruder exposure. However, multiparity increased oxytocin/CRFR1 co-expression relative to primiparous and nulliparous mice in the paraventricular hypothalamus (PVN) and supraoptic nucleus (SON). Multiparous mice also showed elevated CRFR1-GFP in the PVN and SON relative to primiparous mice. In the medial preoptic area and anteroventral periventricular nucleus, primiparous, but not multiparous mice differed in CRFR1-GFP levels relative to nulliparous mice. Together, these findings indicate dynamic changes in CRFR1 with multiparity that may contribute to stress-related behavior changes.
A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.
Maloney SE, McCullough KB, Chaturvedi SM … +7 more , Selmanovic D, Chase R, Chen J, Wu S, Granadillo JL, Kroll KL, Dougherty JD
Horm Behav · 2025 Aug · PMID 40729938 · Full text
The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. MYT1L haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability,...
The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. MYT1L haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism, behavioral disruptions, aggression, obesity and epilepsy. While MYT1L is expressed throughout the brain, how it supports proper neuronal function in distinct regions has not been assessed. Some features of MYT1L Neurodevelopmental Syndrome suggest disruption of hypothalamic function, such as obesity and endocrine issues, and previous research showed changes in hypothalamic neuropeptide expression following knockdown in zebrafish. Here, we leveraged our heterozygous Myt1l mutant, previously shown to recapitulate aspects of the human syndrome such as hyperactivity, social challenges, and obesity, to examine the impact of MYT1L loss on hypothalamic function. Examining the molecular profile of the MYT1L haploinsufficient hypothalamus revealed a similar scale of disruption to previously studied brain regions, yet with region-specific roles for MYT1L, including regulation of neuropeptide systems. Alterations in oxytocin and arginine vasopressin cell numbers were also found. Behaviors studied included maternal care, social group hierarchies, and aggression, all of which were unchanged. Feeding and metabolic markers were also largely unchanged in MYT1L haploinsufficient mice, yet an interaction was observed between diet and MYT1L genotype on weight gain. Our findings here suggest that gross endocrine function was not altered by MYT1L haploinsufficiency, and that key sex-specific behaviors related to proper hypothalamic function remain intact. Further study is needed to understand the functional impact of the altered hypothalamic molecular profile and changes in neuropeptide cell numbers that result from MYT1L haploinsufficiency.
Birth controlling your fears: The long-term effects of adolescent exposure to hormonal contraceptives on fear extinction in long-evans female rats.
Brooke M, Graham BM
Horm Behav · 2025 Aug · PMID 40729937 · Publisher ↗
The mechanisms involved in inhibiting fear to a threatening cue can be studied in the laboratory via fear extinction, which is a process thought to underpin the development and treatment of anxiety disorders. In adult fe...
The mechanisms involved in inhibiting fear to a threatening cue can be studied in the laboratory via fear extinction, which is a process thought to underpin the development and treatment of anxiety disorders. In adult female rats, fluctuating sex hormones across the estrous cycle modulate fear extinction, and suppressing sex hormones via hormonal contraceptives (HCs) impairs fear extinction. Despite high usage of HCs during adolescence, no research has examined HC effects on extinction during this developmental phase. In the current study, adolescent female rats (postnatal day 35) were administered a nine day treatment of one of two HC formulations: a high dose of levonorgestrel (LEV), or a lower dose of LEV combined with ethinyl estradiol (EE). Rats received fear conditioning, extinction training, and extinction retention, either across the last few days of HC exposure, or two weeks post HC-cessation as adults (postnatal day 58). In both adolescents and adults, LEV impaired extinction retention, but EE + LEV did not. Altogether, these findings provide evidence that LEV impairs extinction retention during adolescence, and that this impairing effect lasts beyond the cessation of LEV when exposure begins during adolescence. Both HC formulations suppressed endogenous sex hormones during HC exposure, and neither produced long-term effects on endogenous sex hormones two weeks post cessation, suggesting that suppression of endogenous hormones were not the sole mechanism for the impairing effects of LEV on extinction retention. Such findings may have implications for the potential impact of HC use during adolescence on the development and treatment of anxiety disorders.
Sex difference in the effects of ventral pallidum vasopressin 1a receptor partial knockdown on social behavior in mice.
Friesen CN, Hartswick D, Selke A … +2 more , de Vries GJ, Petrulis A
Horm Behav · 2025 Aug · PMID 40716389 · Full text
The neuropeptide vasopressin (AVP) regulates a diverse array of social behaviors, often having different functions in males and females. This sex difference is due, in part, to the AVP cells in the bed nucleus of the str...
The neuropeptide vasopressin (AVP) regulates a diverse array of social behaviors, often having different functions in males and females. This sex difference is due, in part, to the AVP cells in the bed nucleus of the stria terminalis (BNST), which are more numerous in males than in females. These AVP cells send stronger projections to several brain regions that express the vasopressin 1a receptor (V1aR), including the ventral pallidum (vPal), an area broadly implicated in reward-seeking behavior. Previous experiments manipulating V1aR in vPal have found that activation of V1aR in this area mediates AVP effects on social behavior with differential effects on male and female rats across different social contexts. Consequently, to better understand the role of V1aR in vPal, we reduced V1aR expression in the vPal using a viral-mediated RNA-interference approach in male and female mice and tested their social investigatory, aggressive, copulatory and communicative responses to male and female conspecifics as well as their responses to anxiogenic or rewarding stimuli. Partial knockdown of V1aR in vPal of males reduced their social investigation of other males, but not of females, whereas the same manipulation had no effect on social investigation in females. In addition, partial knockdown in males reduced latencies to ejaculate during copulation. Reduction in V1aR within vPal did not influence communicative and aggressive behaviors, urine investigation, anxiety-like behavior, or sucrose preference. These results suggest that V1aR activity in the vPal specifically facilitates intermale investigation in adult mice but normally dampens their ejaculatory behavior.
Chronic periadolescent leuprolide exposure affects the expression of multiple genes in the hypothalamus and pituitary gland with a different pattern of expression in female and male Long-Evans rats.
Guarraci FA, Klepcyk IM, Thompson LM … +5 more , Streifer M, Hilz EN, Hudson G, Meerts SH, Gore AC
Horm Behav · 2025 Aug · PMID 40712505 · Publisher ↗
Protracted exposure to drugs like Lupron Depot® suppresses pubertal development. How the brain responds and develops in the face of pharmacological suppression is not well understood. The present study tested the effects...
Protracted exposure to drugs like Lupron Depot® suppresses pubertal development. How the brain responds and develops in the face of pharmacological suppression is not well understood. The present study tested the effects of daily leuprolide acetate (LEU) treatment (50 μg/kg, postnatal day (PD) 25-50) on gene expression (Kiss1, Esr1, Esr2, Ar, Gnrh1, Gnrhr) in the hypothalamus and pituitary of female and male Long-Evans rats using real-time PCR. Brains and trunk blood were harvested on PD 50. In the pituitary gland of both sexes, expression of Esr2 and Gnrhr expression was higher in LEU-treated rats than in saline controls. Esr1 expression in females was lower and Ar expression in males was higher in LEU-treated rats than saline controls. In the preoptic area of the hypothalamus in male rats, Kiss1 expression was significantly lower in LEU than in saline controls. In the mediobasal hypothalamus, Gnrh1 and Kiss1 expression was higher in LEU-treated male rats than in saline controls; for females, only Kiss1 was increased by LEU. Serum gonadal hormone levels were not significantly different in LEU-treated rats than saline controls at the end of treatment, although hormones trended lower in the LEU-treated rats. LEU affected expression of genes involved in reproduction, potentially explaining sex-specific effects of LEU on behavior reported earlier. The changes in hypothalamic and pituitary gene expression may represent compensation that permits early stages of pubertal development (e.g., VO and PPS), but not complete maturation (e.g., estrous cyclicity, sexual behavior) during LEU treatment.
A dopamine agonist affects the social decision-making of calling male túngara frogs.
James LS, Woolley SC, Ryan MJ
Horm Behav · 2025 Aug · PMID 40706147 · Publisher ↗
When vocalizing, many animals engage in decision-making processes that integrate information regarding the current social context. The midbrain dopaminergic system may provide a conserved mechanism underlying this proces...
When vocalizing, many animals engage in decision-making processes that integrate information regarding the current social context. The midbrain dopaminergic system may provide a conserved mechanism underlying this process. For instance, in songbirds, modulation of dopamine release appears to contribute to social context-dependent changes to song. However, relatively little is known about the degree to which dopamine may contribute to similar vocal production and decision-making processes in other taxa, particularly the highly vocal anurans (frogs and toads). Here, we treated wild-caught male túngara frogs (Engystomops pustulosus) with a general dopamine agonist (apomorphine) and assessed its effects on motor performance and motivation as well as vocal decision-making in response to auditory stimuli that varied in social relevance. We found that the dopamine agonist generally increased vocal speed, with decreases in response latencies and call durations. Additionally, we found that dopamine increased call complexity, but only in response to the most socially relevant auditory stimulus (conspecific call). Finally, dopamine treatment and auditory stimulus interacted to affect decision-making regarding call timing and overlap with the stimulus. Compared to controls, frogs with apomorphine were more likely to overlap the playback stimulus in a manner predicted to be more attractive to females. These results highlight a role of dopaminergic circuits in modulating vocal outputs based on social inputs within a species of basal tetrapod.
Hormonal and sex-specific functional genomic pathways of genetic risk candidates in autism spectrum disorder: evidence of sex-over-chance effects.
Briones-Valdivieso C, Córdova F, Kaune H … +1 more , Montiel JF
Horm Behav · 2025 Aug · PMID 40706146 · Publisher ↗
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by substantial sex differences in prevalence, with males more frequently diagnosed than females. While genetic and environmental factors con...
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by substantial sex differences in prevalence, with males more frequently diagnosed than females. While genetic and environmental factors contribute to ASD, there is growing evidence that sex-specific endocrine pathways, particularly those involving sex hormones, may play a critical role in ASD etiology. This study aimed to investigate the functional network robustness and annotations of autism spectrum disorder genetic risk candidates (ASD-GRCs), with a focus on endocrine pathways and their impact on network connectivity. Using data from the Simon's Foundation Autism Research Initiative (SFARI) and functional network analysis via the STRING database, we assessed the connectivity of ASD-related genes by randomly subtracting sets of genes from the whole ASD gene network in subsets associated with androgen-testosterone, estrogen-progesterone, and other hormone pathways. Our findings reveal a significant "sex-over-chance" association, with androgen- and estrogen-related gene subsets showing marked connectivity within the ASD gene network compared to non-sex hormone genes. These results suggest that sex hormones may uniquely influence ASD-related neural development, providing support for the "female protective effect" and the androgen-driven model of ASD. Additional analyses of other hormonal pathways, such as oxytocin and cortisol, showed a lower connectivity impact, reinforcing the distinctive role of sex hormones in ASD. This study highlights the potential of endocrine-focused genetic analysis in understanding ASD, emphasizing sex-specific biological mechanisms that may inform future diagnostic and therapeutic strategies.
Mineralocorticoid receptor deletion alters spontaneous behavior in an automated home-cage monitoring apparatus.
Kendricks DR, Sleiman SJ, Fry SA … +8 more , Stallone J, Bernstein BJ, Stevanovic KD, Aksu LR, Alexander GM, McCann KE, Dudek SM, Cushman JD
Horm Behav · 2025 Aug · PMID 40695223 · Full text
Mineralocorticoid receptors (MRs) are transcription factors expressed throughout the body and brain, with especially high expression in the hippocampal area CA2. MRs are essential for maintaining the physiological stress...
Mineralocorticoid receptors (MRs) are transcription factors expressed throughout the body and brain, with especially high expression in the hippocampal area CA2. MRs are essential for maintaining the physiological stress response and regulating the hypothalamic-pituitary adrenal (HPA) axis. Further, MRs function through the diurnal modulation of corticosterone activity. The aim of the current study was to determine the role MRs play in the modulation of spontaneous behavior throughout the day/night cycle. Three conditional MR knockout mouse lines were utilized: one with broad embryonic neuronal deletion (Nestin-Cre), one with embryonic forebrain deletion (EMX-Cre), and one with postnatal CA2-targeted deletion (Amigo2-Cre). Behavior in these strains was assessed using an automated home cage monitoring system to track spontaneous behavior over a 60-h period. Broad deletion of MRs disrupted behavior in a sex-dependent manner, with alteration in motor activity and shelter behavior at night. Forebrain deletion of MRs produced similar, but less pronounced, differences in motor activity and shelter behavior, while CA2-targeted deletion produced little alteration in behavior either during the day or at night. These findings provide evidence for the essential role of MRs in the regulation of behavior across the day/night cycle and shed a light on the role of MR development and expression on behavior.
Conspecifics confer survival advantage in the face of night-light polluted environment: Evidence from melatonin secretion, sleep, mood and cognitive performance in Indian house crows.
Buniyaadi A, Bhardwaj SK, Kumar V
Horm Behav · 2025 Aug · PMID 40680373 · Publisher ↗
The survival advantage of group living remains poorly understood. Here, this was investigated by using several physiological and neurobehavioral traits in Indian house crows (Corvus splendens) in the face of a temporally...
The survival advantage of group living remains poorly understood. Here, this was investigated by using several physiological and neurobehavioral traits in Indian house crows (Corvus splendens) in the face of a temporally disrupted day-night environment. Crows were housed singly or with two other conspecifics and subjected to daily 12-h light and 12-h periods of complete (0 lx) or dimly lighted (∼6 lx) dark nights. Nocturnal melatonin and sleep levels were measured as indices of the direct and circadian effects, while mood (feeding, preening, and self-mutilation) and cognition (innovative problem-solving task) performances were considered reflecting the higher-order brain function effects. Under 6-lx dim light at night (dLAN) condition, group housing alleviated the depressive-like responses and enhanced cognitive performance but had no effect on the midnight melatonin levels and nocturnal sleep consolidation. Concurrently, there were increased nr4a2 and decreased tnfr1 gene expressions in hippocampus, increased dcx and darpp-32 gene expressions in the nidopallium caudolaterale, and th expression in midbrain. We interpret that an increased conspecific interaction improved mood and cognitive performance without affecting the melatonin secretion and sleep in communally roosting house crows. Perhaps, living with conspecifics is part of an overall evolutionary strategy to enhance the survival in a highly social species like the Indian house crow.
Spatial and verbal performance relate to the duration of combined oral contraceptive use but do not change during the pill-free interval.
Noachtar I, Pletzer B
Horm Behav · 2025 Aug · PMID 40674917 · Publisher ↗
BACKGROUND: Ovarian hormones and testosterone have been related to verbal and spatial processing. Oral contraceptives are taken by approximately 150 million women worldwide often for extended time periods. To date, the l...
BACKGROUND: Ovarian hormones and testosterone have been related to verbal and spatial processing. Oral contraceptives are taken by approximately 150 million women worldwide often for extended time periods. To date, the literature on long-term effects of COCs on cognition is sparse, and results and methodology are inconsistent. OBJECTIVES: In this manuscript we examined whether verbal and spatial performance changed (i) during short-term hormonal withdrawal as during the monthly pill pause and (ii) related to the duration of COC-use. We assessed the moderating effects of progestin type (androgenicity) and task complexity. METHODS: 180 participants (60 androgenic COC-users, 60 anti-androgenic COC-users and 60 non-users with a menstrual cycle) were tested once during their active pill phase/luteal phase and once during their pill pause/menses. We compared mental rotation, navigation and verbal fluency performance between the pill pause and active intake phase in COC users and assessed how the differences compared to fluctuations along the menstrual cycle in naturally cycling women. RESULTS: No differences between active pill intake and pill pause were found in mental rotation, navigation or verbal fluency in long-term users. Irrespective of COC-phase, androgenic COC-users demonstrated higher orientation accuracy compared to anti-androgenic COC-users and non-users. Longer pill duration was associated with better orientation accuracy and decreased phonemic word and switching production in COC-users independent of the pill's androgenicity. CONCLUSION: The association of verbal and spatial performance to COC use duration in the absence of short-term changes during the pill-free interval may hint at cumulative effects of long-term COC-use on spatial and verbal processing.
Exposure to novel females increases fecundity in adult male prairie voles.
Hurd JA, Watanabe YL, Toben GJ … +6 more , Ford AK, Miller CA, Sergott CE, Kelley D, Donaldson ZR, McCullagh EA
Horm Behav · 2025 Aug · PMID 40627990 · Full text
Social circuitry of the mammalian brain can influence male reproductive physiology. This often manifests as plasticity in sperm production or allocation, particularly in response to male-male competition. However, social...
Social circuitry of the mammalian brain can influence male reproductive physiology. This often manifests as plasticity in sperm production or allocation, particularly in response to male-male competition. However, socially mediated testicular plasticity has not been investigated with respect to mating and parental strategy. Testis mass and sperm production of sexually naïve and female-exposed adult male individuals of three rodent species were compared: the socially monogamous and paternal prairie vole (Microtus ochrogaster), the promiscuous meadow vole (Microtus pennsylvanicus), and the promiscuous house mouse (Mus musculus). Monogamously paired prairie vole males exhibited significantly larger testes and greater sperm production than naïve prairie vole males. Comparatively, there were no significant differences between naïve and monogamously paired male meadow voles or mice. To investigate the role of olfactory cues for regulating this phenomenon in prairie voles, a group of naïve males exposed to soiled bedding from novel females was used. These males were more similar to paired males than to naïve males not exposed to novel female odors, demonstrating a strong role of the social olfactory system. Further, the predictions of sperm competition theory (species with greater female promiscuity have larger testes than closely related species with less female promiscuity) are not observed between prairie voles and meadow voles. This demonstrates the complexity of intraspecies social dynamics and reproductive pressures which socially monogamous paternal males face and the evolutionary adaptations that may develop in response.
Sex- and site-specific effects of GPER-1 activation on saccharin vs cocaine preference in male and female rats.
Turner CA, Becker JB
Horm Behav · 2025 Jul · PMID 40554072 · Full text
Estradiol (E2) receptor signaling has a sex-specific impact on the brain's reward pathway, enhancing cocaine reinforcement in females but not in males. Selective activation of G-Protein Coupled Estradiol Receptor 1 (GPER...
Estradiol (E2) receptor signaling has a sex-specific impact on the brain's reward pathway, enhancing cocaine reinforcement in females but not in males. Selective activation of G-Protein Coupled Estradiol Receptor 1 (GPER-1) in the dorsolateral striatum (DLS) attenuates the reinforcing effects of 0.1 % saccharin (SACC) and cocaine in males but not females. This study investigated GPER-1 activation in the DLS and systemically using the GPER-1 agonist G1 to assess its effect on SACC and cocaine preference in male and female rats. Five experiments were conducted using gonad-intact and gonadectomized animals to determine dose-response effects and the influence of circulating hormones. Intra-DLS GPER-1 activation with 20 % G1 selectively reduced SACC preference in intact males but not females, while higher and lower concentrations had no effect. Systemic G1 administration attenuated cocaine-induced conditioned place preference (CPP) in both sexes in a dose-dependent way. Interestingly, systemic administration of G1 did not alter SACC preference in either sex, regardless of the presence or absence of gonadal hormones. These findings suggest that GPER-1 activation influences reward processing in a site-, reward-, and sex-dependent manner.
Maternal immune activation during the lactational period alters offspring behavior, reproductive development, and immune function in mice.
Merengueli JA, Kentner AC
Horm Behav · 2025 Jul · PMID 40543230 · Full text
Exposure to infection during early life can lead to lasting neurodevelopmental changes. Animal models of maternal immune activation (MIA) typically assess neurobehavioral alterations in offspring following a prenatal inf...
Exposure to infection during early life can lead to lasting neurodevelopmental changes. Animal models of maternal immune activation (MIA) typically assess neurobehavioral alterations in offspring following a prenatal inflammatory challenge. However, MIA effects on offspring can extend to challenges that occur during the lactational period. In the present study, we adapted previous methods focused on rats and challenged nursing C57BL/6J mouse mothers on postnatal day (P)8 with either the bacterial mimetic lipopolysaccharide (LPS; 250 μg/kg, i.p.) or saline (control, i.p.). By exposing only the mother to LPS, this modeled a postpartum infection in the dam. Similar to the rat model, lactational MIA did not detrimentally alter maternal care but induced displays of maternal sickness, as expected. While neonatal offspring behaviors (e.g., huddling, ultrasonic vocalizations, negative geotaxis) were unaffected, significant effects of lactational MIA emerged in juvenile (e.g., social preference, accelerated reproductive milestones) and adult (e.g., mechanical allodynia, prepulse inhibition) offspring. In a separate set of animals, the developmental programming potential of lactational MIA on immune function was evident following a "second hit" LPS challenge in adulthood (e.g., altered plasma concentrations of interleukin-6 and leukocytes, including neutrophils, and lymphocytes). These findings confirm the generalizability of the lactational MIA model across species and highlight the importance of supporting caregiver health and wellness across the critical nursing period.
Behavioral sex differences in the developmental emergence and selectivity of partner preferences in prairie voles.
Schaepe CA, Hiura LC
Horm Behav · 2025 Jul · PMID 40532532 · Full text
Convergent evidence across foundational and clinical research has demonstrated the expansive functions and health consequences of adult pair bonding. For decades now, study of the socially monogamous prairie vole (Microt...
Convergent evidence across foundational and clinical research has demonstrated the expansive functions and health consequences of adult pair bonding. For decades now, study of the socially monogamous prairie vole (Microtus ochrogaster) has provided valuable mechanistic insights into the neuromolecular substrates that enable adult pair bond formation and maintenance. Despite this rapidly growing literature, substantially less is known about the lifespan development of pair bonding behavior and the organization of the monogamous brain. To characterize the age at which prairie voles are capable of pair bonding, we tested if male and female prairie voles between juvenile and adult stages of development could exhibit an other-sex partner preference after 48 h of cohabitation. We found that females paired by early adolescence (P31-36) preferred to huddle with their partner over a novel male conspecific, but this selective social preference was not observed in males until adulthood (P60+). Further, the degree of preference for the pair bond partner was greater in females compared to males, suggesting that there is a robust sex difference in the developmental onset and strength of pair bonding in this species. Identifying the typical developmental trajectories of sex-specific pair bonding behavior will enable novel inquiries into the neuroscience and endocrinology of age-specific social attachments.
Not your mother's hormone therapy: Highly selective estrogen receptor beta agonists as next-generation therapies for menopausal symptom relief.
Frick KM, Fleischer AW, Schwabe MR … +3 more , Abdelazim FA, Sem DS, Donaldson WA
Horm Behav · 2025 Jul · PMID 40482564 · Full text
Although the menopausal transition causes a panoply of unpleasant and disruptive symptoms, many women are reluctant to use estrogen-based treatments due to risks of cancer, cardiovascular disease, and stroke. As we learn...
Although the menopausal transition causes a panoply of unpleasant and disruptive symptoms, many women are reluctant to use estrogen-based treatments due to risks of cancer, cardiovascular disease, and stroke. As we learn more about how estrogens regulate the cellular and circuit mechanisms underlying menopausal symptoms such as hot flashes and brain fog, drug development that specifically targets these mechanisms could provide the therapeutic benefits of estrogens without adverse health effects. This review discusses the rationale for targeting estrogen receptor beta (ERß) with highly selective synthetic agonists to alleviate two common menopausal symptoms: memory dysfunction and hot flashes. We begin by reviewing the history of estrogen-based menopausal hormone therapy, including conjugated equine estrogens and related products. We then describe the neurobiological mechanisms underlying estrogenic regulation of memory and hot flashes, with a particular focus on the role of ERß. Finally, we discuss past and current clinical trials of ERß agonists and highlight pre-clinical data showing that a highly potent and selective synthetic ERß agonist can enhance object recognition and spatial memory, and reduce a drug-induced hot flash, in mouse models of ovarian hormone loss and Alzheimer's disease. Collectively, this work supports the targeted development of highly selective ERß agonists to relieve memory and vasomotor symptoms of menopause.
Effects of racial discrimination tasks on salivary cortisol reactivity among racially minoritized groups: A meta-analysis.
Obomsawin A, Pejic SR, Koziol C
Horm Behav · 2025 Jul · PMID 40482563 · Publisher ↗
RATIONALE: Racial discrimination can be specifically defined as the differential treatment of an individual or group based on their racial identity. Increasingly, the experience of racial discrimination is characterized...
RATIONALE: Racial discrimination can be specifically defined as the differential treatment of an individual or group based on their racial identity. Increasingly, the experience of racial discrimination is characterized as a social stressor that elicits physiological responses and increases the risk of poor health over the lifespan. However, recent attempts at synthesizing the literature surrounding racial discrimination and cortisol output, specifically, have produced mixed results. This is likely due to the inclusion of broad research designs (e.g., cross-sectional, experimental), measures of cortisol activity, and measures of racial discrimination. OBJECTIVES: The primary goal of the current study was to apply a narrow lens to the synthesis of the racial discrimination and cortisol output literature. Specifically, by examining the association between acute racial discrimination and salivary cortisol reactivity, we aimed to demonstrate a clear pattern within the research area. RESULTS: Using five studies (composed of seven unique datasets; N = 650), we conducted a random effects model using the CMA software. Results indicate that racial discrimination stressors are associated with elevated acute cortisol levels (standard difference in means = 0.189, 95 % CI [0.083, 0.295]). CONCLUSION: By approaching the literature with a narrow lens, this meta-analysis provides support for the association between acute experiences of racism and salivary cortisol reactivity. Findings also demonstrate a clear need for future research and highlight the influence of methodological decisions on synthesis efforts.
Apelin-13 elicits lordosis behavior in female rats through the oxytocin/prostaglandin E2/GnRH signaling system.
Domínguez-Ordóñez R, García-Juárez M, Encarnación-Sánchez JL … +5 more , Téllez-Angulo B, Palafox-Moreno J, Luna-Hernández A, Pfaus JG, González-Flores O
Horm Behav · 2025 Jul · PMID 40472452 · Publisher ↗
The present study investigated the role of the oxytocin (OT)/prostaglandin E2 (PGE2)/gonadotropin-releasing hormone (GnRH) and the progesterone receptor (PR) pathways in facilitating lordosis behavior induced by intrahyp...
The present study investigated the role of the oxytocin (OT)/prostaglandin E2 (PGE2)/gonadotropin-releasing hormone (GnRH) and the progesterone receptor (PR) pathways in facilitating lordosis behavior induced by intrahypothalamic administration of 0.75 μg of apelin-13 in ovariectomized (OVX) rats primed with estradiol benzoate (EB). To explore this pathway, various inhibitors were administered bilaterally into the ventromedial hypothalamus (VMH) of EB-primed rats 30 min before the infusion of apelin-13. The inhibitors used included atosiban (ATO), an OT receptor antagonist; acetylsalicylic acid (aspirin), a cyclooxygenase-2 (COX-2) inhibitor; ONOAE3-208 (ONO), a PGE2 receptor antagonist; RU486, an antiprogestin for the PR; and antide, a GnRH-1 receptor antagonist. Apelin-13 at this dosage used, consistently induced lordosis at 30, 120, and 240 min post-infusion. The administration of atosiban, ONO, antide, and RU486, significantly reduced both the lordosis quotient (LQ) and lordosis reflex score (LS) at all assessed time points. In contrast, aspirin only decreased the LQ at 30 and 120 min, while the LS was reduced at all times tested. Because the OT/PGE2/GnRH pathway has been widely demonstrated in hypothalamic astrocytes as a regulator of GnRH release, it may also play a role in regulating female sexual behavior in estradiol-pretreated rats.
Altered regional gray matter in Congenital Adrenal Hyperplasia (CAH).
Luders E, Spencer D, Gaser C … +6 more , Thankamony A, Hughes I, Srirangalingam U, Gleeson H, Hines M, Kurth F
Horm Behav · 2025 Jul · PMID 40472451 · Full text
Congenital Adrenal Hyperplasia (CAH) has been reported to present with gray matter aberrations, but further research is required as the results of existing studies are inconsistent. These inconsistences might be due to s...
Congenital Adrenal Hyperplasia (CAH) has been reported to present with gray matter aberrations, but further research is required as the results of existing studies are inconsistent. These inconsistences might be due to small sample sizes, differences in sample composition (some studies only included females), or the spatial scale of the analyses (some studies focused on selected regions of interest). Here we compiled the largest CAH sample to date comprising 33 women and 20 men matched to 33 control women and 20 control men on sex, age, education, and verbal intelligence. Gray matter was examined with a voxel-wise regional specificity across the entire brain, assessing the main effects of CAH and sex, and the CAH-by-sex interaction (the latter reflecting effects of prenatal androgen exposure). Individuals with CAH had significantly less gray matter compared to controls within the amygdala, calcarine cortex (specifically the primary visual area), and parahippocampal cortex (specifically the subiculum). There also was a main effect of sex, with more gray matter in females than males in medial frontal regions and more gray matter in males than females within the cerebellum. There was no CAH-by-sex interaction. Our findings indicate less regional gray matter in individuals with CAH, which seems to be caused by the medical condition itself and/or its treatment with glucocorticoids, rather than by elevated prenatal androgen exposure.
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