Mapping the developmental trajectory of stress effects: pubescence as the risk window.

The exposure to stress at different developmental time points has long been postulated to have a crucial impact on various brain structures involved in mental disorders. The long-term specific effects seem to emerge as a function of timing and duration of the exposure to stress, as well as the characteristics of the stressor. Previous studies have addressed this issue with an effort to describe a single "hyper-sensitive" time point, and have led to disagreement on a particular sensitive period for stress exposure. The primary aim of our study was to investigate the hypothesis that indeed there is a developmental stress risk window in male Wistar rats. We conducted a systematic mapping of the long-term effects of an acute stress protocol, applied both prenatal (gestational days 14-16) and postnatal (days 9-151), overall at 11 different time-points during development. Stress protocol consists of 3 days of either maternal separation (for rats at postnatal days 9-19) or exposure to the stressors forced swim, elevated plus maze and restraint (for both dams and males at postnatal days 24-151). Consequences in adulthood were measured by investigating the animals' behavior in both the open field and startle box, together with the physiological measure of corticosterone. We found both behaviorally and physiologically that the pubescence time points are the most vulnerable to stress compared to all other tested time points along the developmental trajectory. Carefully considering the comparison between rat and human age, our findings may imply the importance of childhood-to-adulthood transition, as a sensitive time-point which may exacerbate a predisposition for the development of stress-induced psychopathologies.