Attachment Bond interference and psychopathology: the shelding effect of the earned-secure attachment

Early-life experiences affecting attachment bond can have long-lasting consequences resulting in negative outcomes, such as depression, in adulthood. However, the formation of an earned-secure attachment with an alternative caregiver can act as a protective factor against attachment disruption with the primary caregiver. The Dopaminergic (DA) system of the Ventral Tegmental Area (VTA) is involved in both attachment bond and depression, and it is particularly sensitive to early-life manipulations. VTA DA neurons are characterized by an inward regulatory mechanism, the hyperpolarized-activated cation current (Ih current) and, interestingly, this mechanism was found altered in animal model of depression. We have previously reported that C57BL/6J female mice exposed to Repeated Cross Fostering (RCF), a procedure affecting attachment bond during a sensitive time window, showed resilience to depression and decreased Ih current in VTA DA neurons. However, females by a different inbred strain, DBA/2J (DBA), exposed to RCF, show increased vulnerability to depressive-like behavior in adulthood. Here, we hypothesized that the opposite phenotype observed in DBA females is related to an opposite alteration of Ih current. Moreover, we also hypothesized that by introducing a stable attachment caregiver during RCF, is sufficient to prevent both behavioral and electrophysiological alterations observed in RCF mice. First, we analyzed the Ih current density in VTA DA neurons of adult RCF and Control females thought patch-clamp recording. Then, we performed RCF procedure introducing a Stable Attachment Figure (SAF) that remains with the pups from PND1 to PND4. After assessing pups’ attachment behavior, by analyzing the emitted vocalization while apart from the mother, we tested mice in adulthood to evaluate the rescue effect of SAF on depressive-like phenotype through Forced Swimming Test, Tail Suspension Test and evaluated possible SAF effect on social behavior by Social Interaction Test. Finally, we investigated VTA DA neuron Ih current in RCF+SAF adult females. Our results indicated that depressive-like behavior induced by RCF is linked to increased Ih current density and that rescuing the attachment bond alteration, by providing pups with an alternative stable caregiver is sufficient to prevent these alterations.