Repeated Cross-fostering Protocol as a Mouse Model of Early Environmental Instability

Early life events have a crucial role in programming the individual phenotype indeed the exposure to traumatic experiences during infancy can increase later risks for a variety of neuropsychiatric conditions, including mood and anxiety disorders. Several studies in rodents demonstrated the impact of short and long sessions of separation/isolation from caregivers in developing pups, on the behavioral and hormonal response to stress during infancy and adulthood (D'Amato et al., 1998; Meaney et al., 2000; Luchetti et al., 2015). The repeated cross-fostering (RCF) is an early manipulation carried out in mouse pups during the first four postnatal days life. Differently from other early manipulations, hypotalamic-pituitary-adrenal (HPA) axis functioning is not altered in RCF treated subjects. This manipulation is used to model human early environmental instability, a risk factor for internalizing disorders including separation anxiety disorder, panic disorder and CO2 hypersensitivity (Kendler et al., 1992; Forman and Davies, 2003; Battaglia et al., 2009).