Female zebra finches are more vulnerable to social isolation stress than males: involvement of the nonapeptide system

In group-living animals, chronic social isolation stress (SIS) during the juvenile can profoundly affect behavior and neuroendocrine systems. However, how SIS influences the social behavior of avian species, particularly regarding sex-specific differences at the neural circuit level, remains poorly explored. This study focuses on zebra finches — a species noted for social clustering and cognitive abilities — to reveal significant insights into these effects. We found that SIS increased plasma corticosterone levels in females but not in males, suggesting a higher susceptibility in females. SIS adversely affects sociality and flocking behavior in both sexes, but it has a more pronounced impact on social recognition in females. Mesotocin (MT) levels in the lateral septum of both sexes and the ventromedial hypothalamus of females play an important role in mediating the SIS effect, while vasotocin (VT) levels in the social behavior network remain unaffected. Pharmacological interventions underscore the critical role of MT in reversing SIS-induced impairments in sociality, flocking behavior, and social recognition, particularly in females. Our findings uncover unique nucleus- and sex-dependent variations in MT and VT levels in avian models. This study offers novel insights into sex-specific mechanisms regulating social behavior in birds and contributes to a broader understanding of the independent evolution of neural circuits and neuroendocrine systems that govern social behaviors across different taxonomic groups.