The ghrelinergic system is a key regulator of feeding and metabolism. Beyond this, the ghrelinergic system has been implicated for reward, anxiety and depression. In this regard, the effects of the endogenous ghrelin receptor inverse agonist liver-expressed antimicrobial peptide (LEAP) 2 on mental health parameters are unknown. In the present study, the aim was to delineate LEAP2's central effects on anxiety- and depressive-like behaviors in mice, as well as downstream central monoaminergic signaling and HPA-axis activation. Acute intracerebroventricular administration was used to evaluate the effect of central LEAP2. The anxiogenic and depressive-like effects were measured through open-field test, elevated plus maze and forced swim test. Corticosterone and monoamine levels were measured in ex vivo blood and brain tissues, respectively. Acute central administration of LEAP2 increased anxiety-like behavior in both open-field test and elevated plus maze, and increased immobility time in forced swim test, compared to vehicle. Further, LEAP2 administration was associated with a marked increase in blood corticosterone, elevated dopamine in the bed nucleus of the stria terminalis and a trend to increased serotonin in the nucleus accumbens, ventral tegmental area and hypothalamus. These results highlight the influence of the ghrelinergic system on central signaling and mental health, in particular where LEAP2 is elevated or dysregulated, for example in obesity and anorexia nervosa which are often associated with anxiety and depression. Here, LEAP2 emerges as a potential target to treat depression and anxiety in eating disorders.

Social interactions are vital in animal life, providing access to key information about foraging opportunities, mates, and predators. Yet in highly competitive environments, being social can be costly, as increased interaction rates may lead to more frequent aggressive encounters, favouring the development of more competitive phenotypes. Remarkably, these environmental pressures can have transgenerational effects. For example, mothers can respond to their social environment by transferring non-genetic compounds, such as hormones, to their offspring. However, evidence for an effect of social density on maternal hormone allocation and subsequent offspring social phenotypes remains scarce. Here, we experimentally manipulated social density in the blue tit (Cyanistes caeruleus) by rearranging nest-boxes before egg-laying, thus creating areas of high and low density -and likely high and low competition levels. We measured yolk testosterone and assessed nestling behaviour through a social preference test (sociability) and breathing rate (a proxy for proactivity). As predicted, mothers in low-density areas deposited less testosterone than those in high-density areas. Nestlings raised at low density showed higher sociability, though this effect was male-specific. Breathing rate had a non-linear, positive relationship with yolk testosterone concentration but was, unexpectedly, lower in high-density areas. Together, these findings suggest that competitive environments increase maternal testosterone transfer, likely promoting more competitive and less social offspring phenotypes.

In many cooperatively breeding species non-breeding individuals help to rear the offspring of breeders. The physiological mechanisms that regulate such cooperative helping behavior are poorly understood, but may have been co-opted, during the evolution of cooperative breeding, from pre-existing mechanisms that regulated parental care. Key among these may be a role for prolactin. Here we investigate whether natural variation in circulating prolactin levels predicts both parental and helper contributions to nestling provisioning in wild cooperatively breeding white-browed sparrow weavers, Plocepasser mahali. In sparrow weaver groups, a dominant pair monopolize reproduction and non-breeding subordinates help with nestling feeding. We show that: (i) among parents, females feed their nestlings at higher rates, make longer provisioning visits, and have higher prolactin levels than males; and (ii) among subordinates, engaged in cooperative helping behavior, those within their natal groups feed nestlings at higher rates and have higher prolactin levels than immigrants. Accordingly, continuous variation in prolactin levels positively predicts nestling provisioning rates and provisioning visit durations when all bird classes are combined. These relationships are principally driven by differences among bird classes; the more limited within-class variation in prolactin and provisioning traits were not evidently correlated, for which a range of potential explanations exist. While these correlative findings are broadly consistent with the hypothesis that parental care and cooperative helping behavior are regulated by a shared mechanism, experiments are now needed to establish whether prolactin plays a causal role, and if so, whether it regulates continuous variation in provisioning rate or simply activates provisioning behavior.