Late glucocorticoid receptor antagonism normalizes the enduring effects induced by brief and repeated periods of social isolation stress during early-adolescence

Background: 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 for several weeks from weaning to adulthood. However, the effects induced by brief and repeated periods of SIS only during early-adolescence, a critical phase for brain development, are less explored. Moreover, literature data demonstrated that treatment with glucocorticoid receptor antagonist mifepristone during adulthood normalized effects induced by early-life stress. Methods: Male Sprague-Dawley rats were subjected to two hours of SIS per day during early-adolescence from postnatal day (PND) 28 to PND 34. Adult animals stressed in early-adolescence and their relative control groups were intraperitoneally treated with the glucocorticoid receptor antagonist mifepristone (30 mg/kg) on three non-consecutive days at PND 83, 85 and 87 at adulthood. Then, the enduring behavioral effects induced by brief and repeated periods of SIS during early-adolescence on the emotional domain and the effectiveness of antiglucocorticoid treatment to normalize behavior were evaluated. Results: Our results demonstrated that two hours of SIS from PND 28 to PND 34 induced anxiety-like behavior still present much later in life in the elevated plus maze and acoustic startle response tasks and that treatment with mifepristone at PND 83, 85 and 87 reverted such effects. Conclusions: We found that brief and repeated periods of SIS during early-adolescence profoundly affect behavior at adulthood and that antiglucocorticoid treatment normalizes these behavioral alterations. Additional studies will be performed to better understand the neurobiological underpinnings involved in this process.