Long-term 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. Generally it is conducted for long periods of time from weaning to adulthood. However, the effects induced by repeated brief periods of SIS during early adolescence only, a critical phase for brain development, are less explored. Here, rats were subjected to 2 h of SIS per day from postnatal day (PND) 28 to PND 34. The enduring effects on emotional (elevated plus maze, EPM; open field, OF; acoustic startle response, ASR; marble burying) and cognitive (prepulse inhibition, PPI; Morris water maze, MWM; auditory fear conditioning, AFC) domains were evaluated at adulthood (PND 120-130). We found that brief periods of SIS during early adolescence profoundly affect behaviors at adulthood. 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. We therefore also evaluated whether rats subjected to brief periods of SIS display at adulthood vulnerability (or resilience) for anxiety-like behaviors (EPM, OF, ASR and marble burying) and cognitive deficits (PPI, MWM, AFC) when exposed to a second stress, single prolonged stress (SPS), at adulthood (PND 90). Interestingly, we found that SIS induces resilience towards anxiety-like behavior and vulnerability towards cognitive impairments at adulthood if rats are exposed to SPS. Additional studies will be performed to clarify the neurobiological mechanisms responsible of the increased vulnerability or resilience towards behavioral alterations.