Enduring behavioral effects of brief and repeated periods of social isolation stress during early adolescence

Social isolation stress (SIS) is one of the most commonly used stress paradigm to reproduce psychiatric-like disorders in rodents and it is generally conducted from weaning to adulthood. However, the effects induced by brief and repeated periods of SIS during early adolescence only, a critical phase for brain development, are less explored. Moreover, literature data suggest that early-life adverse experiences may lead to enhanced vulnerability or resilience for stress-related psychopathologies when individuals are exposed to an additional stress later in life. Male Sprague-Dawley rats were subjected to 2 h of SIS per day from postnatal day (PND) 28 to PND 34. The enduring effects on emotional and cognitive domains were evaluated at adulthood (PND 120-130). Moreover, rats were exposed to an additional stress, single prolonged stress (SPS), at PND 90 and the vulnerability (or resilience) for anxiety-like behavior and cognitive deficits were evaluated. Finally, using a stratification approach (20th or 80th percentile in accordance with control group’s distribution), we identified rats with enhanced or reduced susceptibility to the development of specific deficits. Our results demonstrated that SIS induced anxiety-like behavior, but not cognitive impairments at adulthood. Conversely, when rats were subjected to SPS, SIS induced resilience towards anxious-like phenotype and vulnerability towards cognitive impairments at adulthood. We found that SIS profoundly affects behavior at adulthood and that the exposure to an additional stress reverts such effect. Additional studies will be performed in susceptible and resilient rats to better understand the neurobiological underpinnings involved in this process.