Oxytocin Signaling in the Lateral Septum Prevents Social Fear during Lactation.

Oxytocin (OXT)-mediated behavioral responses to social and stressful cues have extensively been studied in male rodents. Here, we investigated the capacity of brain OXT receptor (OXTR) signaling in the lateral septum (LS) to prevent social fear expression in female mice using the social-fear-conditioning paradigm. Utilizing the activated OXT system during lactation, we show that lactating mice did not express fear 24 hr after social fear conditioning. Supporting the role of OXTR signaling in the LS in attenuation of social fear, synthetic OXT infusion or overexpression of OXTR in the LS diminished social fear expression, whereas constitutive OXTR knockout severely impaired social fear extinction in virgin mice. Subsequently, both pharmacological blockade of local OXTRs in the LS and chemogenetic silencing of supraoptic nucleus OXTergic afferents to the LS increased social fear expression in lactating mice. Hence, LS-projecting OXT neurons suppress social fear in female mice.

Salivary oxytocin concentrations in response to running, sexual self-stimulation, breastfeeding and the TSST: The Regensburg Oxytocin Challenge (ROC) study.

Intranasal oxytocin (OXT) application is emerging as a potential treatment for socio-emotional disorders associated with abnormalities in OXT system (re-) activity. The crucial identification of patients with such abnormalities could be streamlined by the assessment of basal and stimulus-induced OXT concentrations in saliva, using a simple, stress-free sampling procedure (i.e. an OXT challenge test). We therefore established the Regensburg Oxytocin Challenge (ROC) test to further validate salivary OXT concentrations as a practical, reliable and sensitive biomarker. OXT concentrations were quantified by radioimmunoassay in samples collected at home by healthy adult male and female volunteers before and after running ("Run") or sexual self-stimulation ("Sex"). In lactating women, salivary OXT concentrations were quantified before, during and after breastfeeding. Salivary OXT along with salivary cortisol and heart rate were monitored in healthy adult participants undergoing the Trier Social Stress Test (TSST). The home-based "Run" and "Sex" challenges as well as the laboratory-based TSST caused quantifiable, rapid, and consistent increases in salivary OXT (approximately 2.5-fold after 10-15min), which were similar for men and women. Breastfeeding did not result in measurably increased salivary OXT levels, probably because the short pulses of OXT release characteristic for lactation were missed. Taken together, ROC tests reliably assess the responsiveness of the OXT system (i.e., the increase in salivary OXT concentrations as compared to basal levels) to challenges such as "Run" and "Sex" at home or psychosocial stress (TSST) in the laboratory. Further studies with larger sample numbers are essentially needed in order to reveal individual differences in ROC test outcomes depending on, for example, genetic or environmental factors.