Oxytocin’s role in depression-like phenotype induced by attachment bond interference

The formation of a stable bond with the attachment figure is one of the most important early life experiences and alterations of this bond are associated with increased vulnerability to several psychopathologies, such as depression, in adulthood. The main neuropeptide involved in social behaviors and attachment bond formation is the Oxytocin (Oxt) and Oxt alterations are reported in depressed patients as well as in animal models of depression.

We have previously demonstrated that Repeated Cross-Fostering (RCF) affects the formation of mother-pup bond and increases vulnerability to depression-like phenotype in C57BL/6J male mice. RCF is an early life manipulation where pups change the mother every 24 hours from PND 1 to PND4.

Here we hypothesized that RCF-induced depression-like phenotype is mediated by a dysregulation of Oxt system.

To test this hypothesis, we analyzed two of the most important targets of the Oxt system: the Oxt Receptor (OxtR) expression in the mesocorticolimbic circuit and the Receptors for Advanced Glycation End-Products (RAGE), an Oxt transporter, across the blood-brain barrier (BBB) of adult RCF and Control mice.

Our results indicate a significant reduction of the OxtR selectively in the Nucleus Accumbens (NAc) and altered levels of RAGE in different BBB cell populations of RCF compared to Control mice.

Finally, to confirm the involvement of the Oxytocinergic system, we precociously treated pups with subcutaneous injections of Oxt during the four days of RCF. This treatment prevented the alteration of attachment bond in pups and the depression-like phenotype in adulthood. In progress experiment are currently investigating the effects of Oxt treatment on OxtR and RAGE.

These data strongly suggest the protective role of Oxt system in mediating appropriate brain and behavioral development.