Behavioral alterations of adolescent rats exposed to prenatal stress: neurobiological mechanisms and implications for psychiatric disorders

Exposure to adverse conditions early in life represents an important risk factor for the development of psychiatric disorders. Adverse perinatal events are indeed associated with profound changes in the progeny, which often become manifest during adolescence. In our studies, we employed the prenatal stress model (PNS) in rats to investigate the behavioral and molecular alterations that develop because of this adverse experience in adolescent rats, also considering sex differences. Pregnant rats were exposed to the prenatal stress (PNS) paradigm from gestational day 14 to birth, while control dams were left undisturbed. During adolescence male and female offspring were exposed to a battery of behavioral tests before sacrifice. We found that PNS exposure produces emotional dysregulation, including anhedonia, anxiety and reduced sociability, in the majority (70%) of male and female adolescent offspring, although 30% of PNS animals were resilient. At the molecular level, we found that such behavioral patterns were associated with selective changes in the expression of activity-dependent genes as well as of immune-related mechanisms in different brain regions including amygdala, dorsal and ventral hippocampus, which are known play a key role in emotional regulation. Moreover, adolescent PNS rats show different responsiveness to an acute stress, suggesting altered ability to cope under a challenging condition. Conclusions - The characterization of the neurobiological mechanisms contributing to resilience or vulnerability to early life stress will be instrumental to identify mechanisms that may be targeted by therapeutic approaches to counteract specific pathologic domains of mental disorders.