Social monogamy is a mating strategy rarely employed by mammalian species. Laboratory studies in socially monogamous prairie voles Microtus ochrogaster demonstrate that oxytocin and vasopressin act within the mesolimbic dopamine pathway to facilitate pair-bond formation. Species differences in oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR) distribution in this pathway are associated with species differences in mating strategy. Here, we characterize the neuroanatomical distribution of OTR and V1aR binding sites in naturally occurring populations of Taiwan voles Microtus kikuchii, which purportedly display social monogamy. Live trapping was conducted at two sites in 2009-2010 and receptor autoradiography for OTR and V1aR was performed on brains from 24 animals. OTR binding in two brain regions where OTR signaling regulates pair-bonding were directly compared with that of prairie voles. Our results show that like prairie voles, Taiwan voles exhibit OTR in the prefrontal cortex, insular cortex, claustrum, nucleus accumbens, caudate-putamen, dorsal lateral septal nucleus, central amygdala and ventromedial hypothalamus. Unlike prairie voles, Taiwan voles exhibit OTR binding in the CA3 field of the hippocampus, as well as the indusium griseum, which has only previously been documented in tuco-tucos Ctenomys haigi, Ctenomys sociabilis, Syrian hamsters Mesocricetus auratus and naked mole-rats Heterocephalus glaber. V1aR binding was present in the ventral pallidum, lateral septum, nucleus basalis, bed nucleus of the stria terminalis, hippocampus, medial amygdala, and anterior, ventromedial and dorsomedial hypothalamus. Marked individual differences in V1aR binding were noted in the cingulate cortex and several thalamic nuclei, remarkably similar to prairie voles. While pharmacological studies are needed to determine whether oxytocin and vasopressin are involved in pair-bond formation in this species, our results lay a foundation for future investigations into the role of these neuropeptides in Taiwan vole social behavior.
Oxytocin modulates many aspects of social cognition and behaviors, including maternal nurturing, social recognition and bonding. Natural variation in oxytocin receptor (OXTR) density in the nucleus accumbens (NAcc) is associated with variation in alloparental behavior, and artificially enhancing OXTR expression in the NAcc enhances alloparental behavior and pair bonding in socially monogamous prairie voles. Furthermore, infusion of an OXTR antagonist into the NAcc inhibits alloparental behavior and partner preference formation. However, antagonists can promiscuously interact with other neuropeptide receptors. To directly examine the role of OXTR signaling in social bonding, we used RNA interference to selectively knockdown, but not eliminate, OXTR in the NAcc of female prairie voles and examined the impact on social behaviors. Using an adeno-associated viral vector expressing a short hairpin RNA (shRNA) targeting Oxtr mRNA, we reduced accumbal OXTR density in female prairie voles from juvenile age through adulthood. Females receiving the shRNA vector displayed a significant reduction in alloparental behavior and disrupted partner preference formation. These are the first direct demonstrations that OXTR plays a critical role in alloparental behavior and adult social attachment, and suggest that natural variation in OXTR expression in this region alone can create variation in social behavior.
Summary
Objective
Clinical and preclinical studies indicate that maternal stress during pregnancy may exert long-lasting adverse effects on offspring. This investigation sought to identify factors mediating the relationship between maternal and neonatal hypothalamic–pituitary–adrenal (HPA) axes in pregnant women with past or family psychiatric history.
Patients
Two hundred and five pairs of maternal and umbilical cord blood samples from a clinical population were collected at delivery.
Measurements
Maternal and neonatal HPA axis activity measures were plasma adrenocorticotrophic hormone (ACTH), total cortisol, free cortisol and cortisol-binding globulin concentrations. The effects of maternal race, age, body mass index, psychiatric diagnosis (DSM-IV), birth weight, delivery method and estimated gestational age (EGA) at delivery on both maternal and neonatal HPA axis measures were also examined. Incorporating these independent predictors as covariates where necessary, we evaluated whether neonatal HPA axis activity measures could be predicted by the same maternal measure using linear regression.
Results
Delivery method was associated with umbilical cord plasma ACTH and both total and free cord cortisol concentrations (T = 10·53–4·21; P < 0·0001–0·010). After accounting for method of delivery and EGA, we found that maternal plasma ACTH concentrations predicted 23·9% of the variance in foetal plasma ACTH concentrations (T = 6·76; P < 0·0001), and maternal free and total plasma cortisol concentrations predicted 39·8% and 32·3% of the variance in foetal plasma free and total cortisol concentrations (T = 5·37–6·90; P < 0·0001), respectively.
Conclusion
These data suggest that neonatal response is coupled with maternal HPA axis activity at delivery. Future investigations will scrutinize the potential long-term sequelae for the offspring.
Context: Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce.
Objective: To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants.
Design, Setting, and Participants: A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternalinfant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n=202), or no psychotropic agents (n=85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face.
Main Outcome Measures: The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials.
Results: Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F2,281=4.51; P=.01; partial η2=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P's<.05) and maternal depression during pregnancy was associated with less efficient habituation (r245=0.16; P<.02). There were no significant differences regarding habituation between medication exposure groups.
Conclusions: Among 6-month-old infants, a history of intrauterine antipsychotic exposure, compared with antidepressant or no psychotropic exposure, was associated with significantly lower scores on a standard test of neuromotor performance, highlighting the need for further scrutiny of the reproductive safety and neurodevelopmental sequelae of fetal antipsychotic exposure. Disentangling medication effects from maternal illness effects, which also contributed, remains a critical challenge.