Fathers today: design of a randomized controlled trial examining the role of oxytocin and vasopressin in behavioral and neural responses to infant signals.

BACKGROUND: Previous research has mostly focused on the hormonal, behavioral and neural correlates of maternal caregiving. We present a randomized, double-blind, placebo-controlled within-subject design to examine the effects of intranasal administration of oxytocin and vasopressin on parenting behavior and the neural and behavioral responses to infant cry sounds and infant threat. In addition, we will test whether effects of oxytocin and vasopressin administration are moderated by fathers' early childhood experiences. METHODS: Fifty-five first-time fathers of a child between two and seven months old will participate in three experimental sessions with intervening periods of one to two weeks. Participants self-administer oxytocin, vasopressin or a placebo. Infant-father interactions and protective parenting responses are observed during play. Functional Magnetic Resonance Imaging (fMRI) is used to examine the neural processing of infant cry sounds and infant threat. A handgrip dynamometer is used to measure use of handgrip force when listening to infant cry sounds. Participants report on their childhood experiences of parental love-withdrawal and abuse and neglect. DISCUSSION: The results of this study will provide important insights into the hormonal, behavioral and neural correlates of fathers' parenting behavior during the early phase of fatherhood. TRIAL REGISTRATION: Dutch Trial Register: NTR (ID: NL8124); Date registered: October 30, 2019.

Vasopressin enhances human preemptive strike in both males and females.

The neuropeptide arginine vasopressin (AVP), which is known to modulate a wide range of social behaviors in animals, has been identified as a modulator of various negative responses to social stimuli in humans. However, behavioral evidence directly supporting its involvement in human defensive aggression has been rare. We investigated the effect of intranasal AVP on defensive aggression in a laboratory experiment, using an incentivized economic game called the "preemptive strike game" (PSG). Participants played PSG individually (1 on 1) as well as in pairs (2 on 2) under either AVP or saline. We observed that exogenous but not basal AVP modulated the attack rate in PSG for both male and female participants. A model-based analysis of the aggregation of individual attack preferences into pair decisions revealed that the AVP effect on defensive aggression occurred mainly at the individual level and was not amplified at the pair level. Overall, these results present the first evidence that intranasal AVP promotes human defensive aggression for both males and females in a bilateral situation where each party can potentially damage the resources of the other party. These findings also parallel accumulating evidence from non-human animals concerning AVP's involvement in territorial defense against potential intruders.

Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice.

Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation is sufficient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVP in the pathogenesis of PE. AVP infusion into pregnant C57BL/6J mice resulted in hypertension, renal glomerular endotheliosis, intrauterine growth restriction, decreased placental growth factor (PGF), altered placental morphology, placental oxidative stress, and placental gene expression consistent with human PE. Interestingly, these changes occurred despite a lack of placental hypoxia or elevations in placental fms-like tyrosine kinase-1 (FLT1). Coinfusion of AVP receptor antagonists and time-restricted infusion of AVP uncovered a mid-gestational role for the AVPR1A receptor in the observed renal pathologies, versus mid- and late-gestational roles for the AVPR2 receptor in the blood pressure and fetal phenotypes. These findings demonstrate that AVP is sufficient to initiate phenotypes of PE in the absence of placental hypoxia, and indicate that AVP may mechanistically (independently, and possibly synergistically with hypoxia) contribute to the development of clinical signs of PE in specific subtypes of human PE. Additionally, they identify divergent and gestational time-specific signaling mechanisms that mediate the development of PE phenotypes in response to AVP.

Bovine neurophysin-II stimulates prolactin release without involvement of dopaminergic prolactin-release inhibiting factor receptor in the estradiol-primed male rat.

Neurophysins have been considered to be physiologically inert carrier proteins for the neurohypophysial hormones, oxytocin and vasopressin. We have observed that bovine neurophysin-II indirectly stimulates prolactin release in estradiol-primed male rats. The release of prolactin is regulated by a dual hypothalamic control system, the prolactin-release-inhibiting factor and the prolactin-releasing factor. We have tried to clarify whether neurophysin-II is acting through stimulation of prolactin-releasing factor by eliminating the possibility of dopaminergic prolactin release-inhibiting factor release. Male rats were primed with estradiol and functional dopaminergic prolactin release-inhibiting factor receptors were completely blocked by pretreatment with a large dose of pimozide (3 mg/kg), a dopaminergic receptor blocking agent. The neurophysin-II stimulated prolactin release in the rats which did not have any functional dopaminergic prolactin release-inhibiting factor receptors suggesting that neurophysin-II likely initiates a chain of events which eventually stimulates prolactin-releasing factor release since the possibility of involvement of the dopaminergic prolactin release-inhibiting factor system is eliminated. Opioids are known to be one of a chain of events which transmit external stress into a stimulation of prolactin release. Naloxone, a mu-receptor antagonist, was injected 20 min before neurophysin-II administration into rats which were primed with estradiol and pretreated with pimozide (3 mg/kg), but the naloxone administration did not block the prolactin release stimulated by neurophysin-II injection. This result indicates that opioids are not one of the chain of events between initiation of stimulation by neurophysin-II and prolactin release.