Involvement of ventral pallidal vasopressin in the sex-specific regulation of sociosexual motivation in rats.

The ventral pallidum (VP) is a critical node of the mesocorticolimbic reward circuit and is known to modulate social behaviors in rodents. Arginine vasopressin (AVP) signaling via the V1A receptor (V1AR) within the VP is necessary for the expression of socially motivated affiliative behaviors in monogamous voles. However, whether the VP-AVP system regulates socially motivated behaviors in non-monogamous species remains unknown. Here, we determined the extent of AVP fiber innervation in the VP as well as the involvement of the VP-AVP system in sociosexual motivation in adult male and female rats. We found that males have nearly twice the density of AVP-immunoreactive (AVP-ir) fibers in the VP compared to females, suggesting the possibility that males experience enhanced AVP signaling in the VP. We further found that this sex difference in VP-AVP-ir fiber density likely arises from an observed sex difference (males > females) in the percentage of VP-projecting AVP-ir cell bodies located in the bed nucleus of the stria terminalis and medial amygdala. To determine the behavioral implications of this sex difference, we next blocked AVP signaling in the VP by antagonizing VP-V1ARs in male and female rats and tested their preference to investigate an unfamiliar male rat or unfamiliar estrus female rat confined to corrals located on opposite ends of a three-chamber apparatus. Under vehicle conditions, males showed a significantly greater innate preference to investigate an opposite sex over same sex conspecific than estrus females. Interestingly, VP-V1AR antagonism significantly reduced males' opposite sex preference, while enhancing estrus females' opposite sex preference. Importantly, all subjects reliably discriminated between male and female stimulus rats regardless of drug treatment, demonstrating a change in motivational state rather than a perceptual impairment induced by VP-V1AR blockade. These results provide a novel functional link between a sex difference in ventral pallidal AVP fiber density and the sex-specific regulation of a sexually motivated behavior necessary for reproductive success.

Quantitative mapping reveals age and sex differences in vasopressin, but not oxytocin, immunoreactivity in the rat social behavior neural network.

The neuropeptides vasopressin (AVP) and oxytocin (OT) have been implicated in the regulation of numerous social behaviors in adult and juvenile animals. AVP and OT signaling predominantly occur within a circuit of interconnected brain regions known collectively as the "social behavior neural network" (SBNN). Importantly, AVP and OT signaling within the SBNN has been shown to differentially regulate diverse social behaviors, depending on the age and/or sex of the animal. We hypothesized that variation in the display of these behaviors is due in part to age and sex differences in AVP and OT synthesis within the SBNN. However, a thorough characterization of AVP and OT-immunoreactive (ir) fibers and cell bodies across age and sex within the SBNN has been lacking in rats. We therefore quantified AVP- and OT-ir fibers and cell bodies in 22 subregions of the forebrain SBNN in juvenile and adult, male and female rats. We found numerous age (16 subregions) and sex (10 subregions) differences in AVP-ir fiber fractional areas, and AVP-ir cell body numbers, which were mainly observed in the medial amygdala/bed nucleus of the stria terminalis to lateral septum circuit. In contrast to AVP, we observed no age or sex differences in OT-ir fiber fractional areas or cell bodies in any of the 22 subregions of the forebrain SBNN. Thus, unlike the static pattern observed for OT, AVP innervation of the forebrain SBNN appears to undergo developmental changes, and is highly sexually dimorphic, which likely has significant functional consequences for the regulation of social behavior.

Microbial lysate upregulates host oxytocin.

Neuropeptide hormone oxytocin has roles in social bonding, energy metabolism, and wound healing contributing to good physical, mental and social health. It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models. We conclude that microbe viability is not essential for regulating host oxytocin levels. The results suggest that a peptide or metabolite produced by bacteria may modulate host oxytocin secretion for potential public or personalized health goals.