Androgens stimulate specific aspects of maternal nest-building and reduce food intake in rabbits

Fluctuations in the plasma concentration of estradiol, progesterone, and prolactin across pregnancy regulate maternal nest-building (digging, straw-carrying, and hair-plucking) and food intake in rabbits. Because testosterone levels also change through pregnancy, we investigated if the injection of testosterone propionate (TP; 1 or 5 mg/day) or 5alpha-dihydrotestosterone propionate (5 or 10 mg/day) for 20 days, alone and combined with progesterone (P; 10 mg/day from days 2 to 15), modulated nest-building and food intake in ovariectomized rabbits. Only the combined injection of TP (5 mg/day) plus P stimulated digging and no treatment promoted straw-carrying or hair-plucking. Both androgens induced hair-loosening from the ventrum, an effect counteracted by P. High doses of TP and 5alpha-dihydrotestosterone propionate reduced food intake by 60-70% of baseline values; this effect was counteracted by P in TP-treated animals. These results support a participation of androgens in specific aspects of maternal nest-building and reveal a strong inhibitory effect on food intake.     

Activational effects of estradiol and dihydrotestosterone on social recognition and the arginine-vasopressin immunoreactive system in male mice lacking a functional aromatase gene

In rodents, parts of the arginine-vasopressin (AVP) neuronal system are sexually dimorphic with males having more AVP-immunoreactive cells/fibers than females. This neuropeptide neuronal system is highly sensitive to steroids and has been proposed to play an important role in the processing of olfactory cues critical to the establishment of a social memory. We demonstrate here that gonadally intact male aromatase knockout (ArKO) mice, which cannot aromatize androgens into estrogens due to a targeted mutation in the aromatase gene, showed severe deficits in social recognition as well as a reduced AVP-immunoreactivity in several brain regions. To determine whether this reduction is due to a lack of organizational or activational effects of estrogens, we assessed social recognition abilities and AVP-immunoreactivity in male ArKO and wild-type (WT) mice when treated with estradiol benzoate (EB) in association with dihydrotestosterone propionate (DHTP) in adulthood. Adult treatment with EB and DHTP restored social recognition abilities in castrated ArKO males since they showed normal female-oriented ultrasonic vocalizations and were able to recognize an unfamiliar female using a habituation-dishabituation paradigm. Furthermore, adult treatment also restored AVP-immunoreactivity in the lateral septum of ArKO males to levels observed in intact WT males. These results suggest that social recognition in adulthood and stimulation of AVP expression in the adult mouse forebrain depend predominantly on the estrogenic metabolite of testosterone. Furthermore, our results are in line with the idea that the organization of the AVP system may depend on androgen or sex chromosomes rather than estrogens.     

Effect of forebrain implants of testosterone or estradiol on scent-marking and sexual behavior in male and female rabbits

Chinning consists of rubbing the chin against an object, thereby depositing secretions from the submandibular glands. As mating, chinning is stimulated in male and female rabbits by testosterone and estradiol, respectively. To investigate the brain sites where steroids act to stimulate chinning and mating we implanted into the ventromedial hypothalamus (VMH) or the medial preoptic area (MPOA) of gonadectomized male and female rabbits testosterone propionate (TP; males) or estradiol benzoate (EB; females) and quantified chinning and sexual behavior. EB implants into the VMH or MPOA reliably stimulated chinning in females. Most of those implanted into the VMH and around half of the ones receiving EB into MPOA or diagonal band of Broca (DBB) showed lordosis. Chinning, but not sexual behavior, was stimulated in males by TP implants into the MPOA or DBB. Neither chinning nor mounting were reliably displayed by males following TP implants into the VMH. Results indicate that, in females, the VMH is an estrogen-sensitive brain area that stimulates both chinning and lordosis while the MPOA seems to contain subpopulations of neurons involved in either behavior. In males, androgen-sensitive neurons of the MPOA, but not the VMH, are involved in chinning stimulation but it is unclear if these areas also participate in the regulation of copulatory behavior.     

Projection from the ventral bed nucleus of the stria terminalis to the retrorubral field in rats and the effects of cells in these areas on mating in male rats versus gerbils

This research identified the rat counterpart of the lateral cell group of the sexually dimorphic area (SDA) found in medial preoptic area (MPOA) gerbil of gerbils. The lateral SDA (lSDA) is critical for mating in male gerbils and contains most of the SDA cells projecting to the retrorubral field (RRF), a projection that is also important for mating. Therefore, to locate the counterpart of the lateral SDA, we traced the inputs to the rat RRF, which were dense in the ventral part of the bed nucleus of the stria terminalis (BST). To determine if the ventral BST or its projection to the RRF affects mating in male rats, we disrupted them bilaterally by placing cell-body lesions bilaterally in the ventral BST or unilaterally there and in the contralateral RRF. We also studied the effects of RRF lesions in both rats and gerbils. Bilateral ventral BST lesions, which left the medial preoptic nucleus intact, produced persistent and severe mating deficits. Disconnecting the ventral BST from the RRF also had long-lasting, but less severe, consequences. RRF lesions produced only temporary mating deficits in rats, but virtually eliminated mating in gerbils. The recovery of mating in rats after RRF, but not ventral BST, lesions, and the intermediate effects of disconnecting these areas from each other suggest that the ventral BST may contain mating-related projection neurons other than those projecting to the RRF or that its RRF-projecting cells send collaterals to another site. In either case, the pedunculopontine tegmental nucleus or raphe nuclei may be involved.     

Vasotocin neurons in the bed nucleus of the stria terminalis preferentially process social information and exhibit properties that dichotomize courting and non-courting phenotypes

Neurons within the medial bed nucleus of the stria terminalis (BSTm) that produce arginine vasotocin (VT; in non-mammals) or arginine vasopressin (VP; in mammals) have been intensively studied with respect to their anatomy and neuroendocrine regulation. However, almost no studies have examined how these neurons process stimuli in the animals' immediate environment. We recently showed that in five estrildid finch species, VT-immunoreactive (-ir) neurons in the BSTm increase their Fos expression selectively in response to positively-valenced social stimuli (i.e., stimuli that should elicit affiliation). Using male zebra finches, a highly gregarious estrildid, we now extend those findings to show that VT-Fos coexpression is induced by a positive social stimulus (a female), but not by a positive non-social stimulus (a water bath in bath-deprived birds), although the female and bath stimuli induced Fos equally within a nearby control region, the medial preoptic nucleus. In concurrent experiments, we also show that the properties of BSTm VT-ir neurons strongly differentiate males that diverge in social phenotype. Males who reliably fail to court females (“non-courters”) have dramatically fewer VT-ir neurons in the BSTm than do reliable courters, and the VT-ir neurons of non-courters fail to exhibit Fos induction in response to a female stimulus.     

Maternal nurturing is dependent on her innate anxiety: the behavioral roles of brain oxytocin and vasopressin

The maternal brain undergoes remarkable physiological and behavioral changes in the peripartum period to meet the demands of the offspring. Here, the brain neuropeptides oxytocin and vasopressin, together with prolactin, play important roles. These neuropeptides are critically involved in the regulation of maternal behavior. Furthermore, reduced anxiety in lactation is another adaptation of the maternal brain. Therefore, a link between maternal behavior and maternal anxiety has been repeatedly postulated. This is supported by our studies in rats bred for high (HAB) and low (LAB) anxiety-related behavior. While female HAB rats become less anxious in lactation, their anxiety level is still four times higher compared with LAB dams. Interestingly, HAB dams display an intense and protective mothering style including increased arched back nursing and pup retrieval whereas LAB dams display only low levels of maternal care. The amount of maternal care directed towards the pups correlates with the mother's innate anxiety. In addition to differences in maternal care, HAB dams are also more protective as they show heightened aggression against a virgin intruder compared with the less aggressive LAB dams. The level of maternal aggression correlates with both their innate anxiety level as well as with the release of oxytocin and vasopressin in hypothalamic and limbic brain areas. Importantly, manipulations of the brain oxytocin and vasopressin systems alter maternal behavior and — depending on the brain region — can also alter the dam's anxiety. Thus, the mother's innate anxiety determines her maternal performance and oxytocin and vasopressin are involved in both parameters.     

Exposure to female pheromones stimulates a specific type of neuronal population in the male but not female magnocellular division of the medial preoptic nucleus (MPN mag) of the Syrian hamster

The magnocellular division of the medial preoptic area (MPN mag) integrates pheromonal and hormonal signals to play a critical role in the expression of male typical sex behavior. The MPN mag contains two morphologically distinct neuronal populations; the percentage of each type within the nucleus is sex specific. Males have more neurons with a single nucleolus whereas females have more with multiple nucleoli. To determine which neuronal subtype mediates pheromonal induction of copulation, tissue from male and female hamsters exposed to female pheromones was immunolabeled for the immediate early protein (EGR-1). Subsequently the tissue was counterstained and the number of ERG-1 neurons with one or two nuclei was determined. The results indicate that pheromones stimulate neurons with single nucleoli in males but fail to stimulate either neuronal subtype in females suggesting that synaptic input to the MPN mag is sexually differentiated.     

Characterization of Extracellular Histamine in the Striatum and Bed Nucleus of the Stria Terminalis of the Rat: An In Vivo Microdialysis Study

The intracerebral microdialysis technique, coupled with a sensitive radioenzymatic assay, was employed to study histamine release in the striatum and in the bed nucleus of the stria terminalis (BNST) in conscious, freely moving rats. In these brain regions, extracellular histamine concentrations decreased by 20% when calcium was omitted from the perfusion solution. Extracellular histamine was insensitive to the addition of tetrodotoxin to the perfusion medium. In striatum, extracellular histamine concentrations declined in an apparent biexponential manner after the administration of alpha-fluoromethylhistidine, an inhibitor of histamine synthesis. The half-lives for the disappearance of histamine were 32 min and 7.7 h, indicating the presence of at least two histamine pools. Histidine loading resulted in a nearly twofold increase in histamine outflow in striatum. In the BNST, yohimbine increased the extracellular histamine content by 50%, suggesting that histamine release is subject to alpha 2-adrenergic regulation in vivo. The extent to which histamine detected in cerebral microdialysis samples is of neurogenic origin remains to be established.     

Organizational effects of estrogens on brain vasotocin and sexual behavior in quail

Reproductive behavior is sexually differentiated in quail: The male-typical copulatory behavior is never observed in females even after treatment with high doses of testosterone (T). This sex difference in behavioral responsiveness to T is organized during the embryonic period by the exposure of female embryo to estrogens. We showed recently that the sexually dimorphic medial preoptic nucleus (POM), a structure that plays a key role in the activation of male copulatory behavior, is innervated by a dense steroid-sensitive network of vasotocin-immunoreactive (VT-ir) fibers in male quail. This innervation is almost completely absent in the female POM and is not induced by a chronic treatment with T, suggesting that this neurochemical difference could be organizational in nature. This idea was tested by injecting fertilized quail eggs of both sexes on day 9 of incubation with either estradiol benzoate (EB) (25 μg, a treatment that suppresses the capacity to show copulatory behavior in adulthood) or the aromatase inhibitor R76713 (10 μg, a treatment that makes adult females behaviorally responsive to T), or with the solvents as a control (C). At 3 weeks posthatch, all subjects were gonadectomized and later implanted with Silastic capsules filled with T. Two weeks later, all birds were perfused and brain sections were processed for VT immunocytochemistry. Despite the similarity of the adult endocrine conditions of the subjects (all were gonadectomized and treated with T Silastic implants providing the same plasma level of steroid to all subjects), major qualitative differences were observed in the density of VT-ir structures in the POM of the different groups. Dense immunoreactive structures (fibers and a few cells) were observed in the POM of C males but not females; EB males had completely lost this immunoreactivity (and lost the capacity to display copulatory behavior); and, conversely, R76713 females displayed a male-typical VT-ir system in the nucleus (and also high levels of copulatory behavior). Similar changes in immunoreactivity were seen in the nucleus of the stria terminalis and in the lateral septum (VT-ir fibers only in this case) but not in the magnocellular vasotocinergic system. These neurochemical changes closely parallel the effects of the embryonic treatments on male copulatory behavior. The vasotocinergic system of the POM can therefore be considered an accurate marker of the sexual differentiation of brain circuits mediating this behavior. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 684–699, 1998     

Paraventricular nucleus lesions abolish the inhibition of feeding induced by systemic cholecystokinin

Peripherally administered cholecystokinin (CCK) initiates a behavioral syndrome which includes reduced food consumption and reduced exploratory behaviors. Previous studies suggest that CCK stimulates receptors in the gut, activating the vagus nerve, which relays sensory information to the nucleus tractus solitarius (NTS) and its ascending pathways. Terminal regions of ascending NTS projections include the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CNA), and the bed nucleus of the stria terminalis (BNST). Lesions of these three target sites were performed in rats to test the hypothesis that structures postsynaptic to the NTS mediate the behavioral syndrome induced by CCK. Knife cut lesions of the PVN abolished the reductions in feeding induced by CCK (5 and 10 micrograms/kg IP), as compared to sham lesioned control rats. PVN lesions only partially attenuated the reductions in exploration induced by CCK (2.5, 5, and 10 micrograms/kg IP), as compared to sham lesioned control rats. Electrolytic lesions of the CNA partially attenuated the reductions in exploratory behavior induced by CCK (2.5, 5, and 10 micrograms/kg IP), and had no effect on the reductions in feeding induced by CCK (5 and 10 micrograms/kg IP). Electrolytic lesions of the BNST had no effect on either the reductions in feeding or the reductions in exploration induced by CCK. The PVN appears to be one critical forebrain target site for mediating the actions of CCK on feeding. The CNA appears to facilitate the actions of CCK on exploration. Individual components of the behavioral syndrome induced by CCK may be mediated by anatomically distinct forebrain loci.     

The bed nucleus of the stria terminalis has developmental and adult forms in mice,with the male bias in the developmental form being dependent on testicular AMH

Canonically, the sexual dimorphism in the brain develops perinatally, with adult sexuality emerging due to the activating effects of pubescent sexual hormones. This concept does not readily explain why children have a gender identity and exhibit sex-stereotypic behaviours. These phenomena could be explained if some aspects of the sexual brain networks have childhood forms, which are transformed at puberty to generate adult sexuality. The bed nucleus of stria terminalis (BNST) is a dimorphic nucleus that is sex-reversed in transsexuals but not homosexuals. We report here that the principal nucleus of the BNST (BNSTp) of mice has developmental and adult forms that are differentially regulated. In 20-day-old prepubescent mice, the male bias in the principal nucleus of the BNST (BNSTp) was moderate (360 ± 6 vs 288 ± 12 calbindin^+ ve neurons, p < 0.0001), and absent in mice that lacked a gonadal hormone, AMH. After 20 days, the number of BNSTp neurons increased in the male mice by 25% (p < 0.0001) and decreased in female mice by 15% (p = 0.0012), independent of AMH. Adult male AMH-deficient mice had a normal preference for sniffing female pheromones (soiled bedding), but exhibited a relative disinterest in both male and female pheromones. This suggests that male mice require AMH to undergo normal social development. The reported observations provide a rationale for examining AMH levels in children with gender identity disorders and disorders of socialization that involve a male bias.     

Organizational effects of testosterone,estradiol, and dihydrotestosterone on vasopressin mRNA expression in the bed nucleus of the stria terminalis

In adulthood, male rats express higher levels of arginine vasopressin (AVP) mRNA in the bed nucleus of the stria terminalis (BST) than do female rats. We tested whether this sex difference is primarily due to differences in neonatal levels of testosterone. Male and female rats were gonadectomized on the day of birth and treated with testosterone propionate (TP) or vehicle on postnatal days 1, 3, and 5 (P1, P3, and P5). Three months later, all rats were implanted with testosterone‐filled capsules. Two weeks later, brains were processed for in situ hybridization to detect AVP mRNA. We found that neonatal TP treatment significantly increased the number of vasopressinergic cells in the BST over control injections. We then sought to determine the effects of testosterone metabolites, estradiol and dihydrotestosterone, given alone or in combination, on AVP expression in the BST. Rat pups were treated as described above, except that instead of testosterone, estradiol benzoate (EB), dihydrotestosterone propionate (DHTP), a combination of EB and DHTP (EB+DHTP), or vehicle was injected neonatally. Neonatal treatment with either EB or EB+DHTP increased the number of vasopressinergic cells in the BST over that of DHTP or oil treatment. However, treatment with DHTP also significantly increased the number of vasopressinergic cells over that of oil treatment. Hence, in addition to bolstering evidence that estradiol is the more potent metabolite of testosterone in causing sexual differentiation of the brain, these data provide the first example of a masculinizing effect of a nonaromatizable androgen on a sexually dimorphic neuropeptide system. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 502–510, 2003     

In vivo comparison of norepinephrine and dopamine release in rat brain by simultaneous measurements with fast-scan cyclic voltammetry

Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. In this study, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the two catecholamines was measured simultaneously using fast-scan cyclic voltammetry at two different carbon-fiber microelectrodes, each implanted in the brain region of interest. Simultaneous dopamine and norepinephrine release was evoked by electrical stimulation of a region where the ventral noradrenergic bundle, the pathway of noradrenergic neurons, courses through the ventral tegmental area/substantia nigra, the origin of dopaminergic cell bodies. The release and uptake of norepinephrine in the vBNST were both significantly slower than for dopamine in the NAc. Pharmacological manipulations in the same animal demonstrated that the two catecholamines are differently regulated. The combination of a dopamine autoreceptor antagonist and amphetamine significantly increased basal extracellular dopamine whereas a norepinephrine autoreceptor antagonist and amphetamine did not change basal norepinephrine concentration. α-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, decreased electrically evoked dopamine release faster than norepinephrine. The dual-microelectrode fast-scan cyclic voltammetry technique along with anatomical and pharmacological evidence confirms that dopamine in the NAc and norepinephrine in the vBNST can be monitored selectively and simultaneously in the same animal. The high temporal and spatial resolution of the technique enabled us to examine differences in the dynamics of extracellular norepinephrine and dopamine concurrently in two different limbic structures.     

Estradiol receptor-alpha expression in hypothalamic and limbic regions of ewes is influenced by physiological state and maternal experience

The influence of estrus, pregnancy, parturition, and maternal experience on the expression of estrogen receptor-alpha (ERalpha) was investigated in hypothalamic and limbic regions of the sheep brain, using immunocytochemistry. Four days before parturition, previous maternal experience was associated with a higher density of ERalpha-labeled neurons in the paraventricular and supraoptic nuclei, the medial preoptic area, and the medial amygdala, but not in the mediobasal hypothalamus. Furthermore, an interaction was found between physiological state and experience in the peripartum period as the effect of experience existing 4 days prepartum was not found at parturition, when densities were lowest both in primiparous and in multiparous ewes. An additional effect of physiological state was also observed between parturition and estrus, densities being significantly lower at parturition than at estrus in the SON, PVN, and MPOA, but not in the medial amygdala. These results indicate that in sheep ERalpha expression is influenced by previous physiological and/or maternal experience at specific times of the reproductive cycle. They are also congruent with the higher ability of multiparous than nulliparous ewes to show maternal behavior several days prepartum.     

Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain

Naked mole-rats (Heterocephalus glaber) are eusocial rodents that live in large subterranean colonies including a single breeding female and 1-3 breeding males; all other members of the colony, known as subordinates, are reproductively suppressed. We recently found that naked mole-rats lack many of the sex differences in the brain and spinal cord commonly found in other rodents. Instead, neural morphology is influenced by breeding status, such that breeders, regardless of sex, have more neurons than subordinates in the ventromedial nucleus of the hypothalamus (VMH), and larger overall volumes of the bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN) and medial amygdala (MeA). To begin to understand how breeding status influences brain morphology, we examined the distribution of androgen receptor (AR) immunoreactivity in gonadally intact breeders and subordinates of both sexes. All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv). We also observed diffuse labeling throughout the preoptic area, demonstrating that distribution of the AR protein in presumptive reproductive brain nuclei is well-conserved, even in a species that exhibits remarkably little sexual dimorphism. In contrast to other rodents, however, naked mole-rats lacked AR+ nuclei in the suprachiasmatic nucleus and hippocampus. Males had more AR+ nuclei in the MeA, VMH, and PMv than did females. Surprisingly, breeders had significantly fewer AR+ nuclei than subordinates in all brain regions examined (VMH, BST, PVN, MeA, and PMv). Thus, social status is strongly correlated with AR immunoreactivity in this eusocial species.     

Breeding-context-dependent relationships between song and cFOS labeling within social behavior brain regions in male European starlings (Sturnus vulgaris)

Male European starlings (Sturnus vulgaris) sing throughout the year, but the social factors that motivate singing behavior differ depending upon the context in which song is produced. In a non-breeding context (when testosterone concentrations are low), starlings form large, mixed-sex flocks and song is involved in flock cohesion and perhaps maintenance of social hierarchies. In contrast, in a breeding context (when testosterone concentrations are high), male song plays a direct role in mate attraction. How the nervous system ensures that song production occurs in an appropriate context in response to appropriate stimuli is not well understood. The song control system regulates song production, learning, and, to some extent, perception; however, these nuclei do not appear to regulate the social context in which song is produced. A network of steroid hormone sensitive nuclei of the basal forebrain and midbrain regulates social behavior. The present study used the immediate early gene cFOS to explore possible involvement of these regions in context-dependent song production. Numbers of cFOS-labeled cells in the medial bed nucleus of the stria terminalis, anterior hypothalamus, and ventromedial nucleus of the hypothalamus related positively only to song produced in a breeding context. In contrast, numbers of cFOS-labeled cells in three zones of the lateral septum related positively only to song produced in a non-breeding context. Taken together, these data suggest differential regulation of male starling song by social behavior nuclei depending upon the breeding context in which it is produced.     

Blood supply of the bed nucleus of the stria terminalis in rat

Summary The topographical distribution of the blood vessels in the bed nucleus of the stria terminalis (NIST) has been mapped in rats. Arteries and veins were visualized in red and blue by using a double-ink perfusion technique. Arteries supplying the NIST arise from the anterior cerebral artery directly or through the anterior communicating and interhemispheric arteries. Only a few, dorsal branches derive from the medial cerebral artery through thalamostriatal arteries. According to their terminal branches, NIST arteries can be divided into five groups: medial, ventral, lateral, septal and dorsal, which have only a relatively small overlap in their territories. About 90% of veins from the NIST drain into the major basal veins. Medial branches run into the perioptic and interhemispheric veins, while the ventral branches and the large lateral vein drain directly into the anterior cerebral vein. A small proportion of NIST veins run dorsalward into the vena cerebri magna via thalamostriatal veins.     

Sex differences in oxytocin receptor binding in forebrain regions: Correlations with social interest in brain region- and sex- specific ways

Social interest reflects the motivation to approach a conspecific for the assessment of social cues and is measured in rats by the amount of time spent investigating conspecifics. Virgin female rats show lower social interest towards unfamiliar juvenile conspecifics than virgin male rats. We hypothesized that the neuropeptide oxytocin (OT) may modulate sex differences in social interest because of the involvement of OT in pro-social behaviors. We determined whether there are sex differences in OT system parameters in the brain and whether these parameters would correlate with social interest. We also determined whether estrus phase or maternal experience would alter low social interest and whether this would correlate with changes in OT system parameters. Our results show that regardless of estrus phase, females have significantly lower OT receptor (OTR) binding densities than males in the majority of forebrain regions analyzed, including the nucleus accumbens, caudate putamen, lateral septum, bed nucleus of the stria terminalis, medial amygdala, and ventromedial hypothalamus. Interestingly, male social interest correlated positively with OTR binding densities in the medial amygdala, while female social interest correlated negatively with OTR binding densities in the central amygdala. Proestrus/estrus females showed similar social interest to non-estrus females despite increased OTR binding densities in several forebrain areas. Maternal experience had no immediate or long-lasting effects on social interest or OT brain parameters except for higher OTR binding in the medial amygdala in primiparous females. Together, these findings demonstrate that there are robust sex differences in OTR binding densities in multiple forebrain regions of rats and that OTR binding densities correlate with social interest in brain region- and sex-specific ways.