Chronic mild corticosterone exposure during adolescence enhances behaviors and upregulates neuroplasticity-related proteins in rat hippocampus.

Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. It remains unknown how adolescent individuals would be affected by chronic exposure to corticosterone (the major stress hormone in rodents, CORT) at the doses that are usually not detrimental in adults. In this study, male Sprague-Dawley rats were injected with CORT (5 mg/kg) or vehicle for 21 days during adolescence (postnatal day (PND) 29-49) or adulthood (PND 71-91) and then subjected to behavioral testing or sacrifice for neurobiological analyses. Shortly after treatment cessation, different from CORT-treated adults showing increased anxiety-like behaviors, CORT-treated adolescents exhibited enhanced prepulse inhibition and spatial learning. They also showed increased expression of hippocampal neuroplasticity-related proteins, including BDNF, nectin3, and AMPA receptor subunits. These effects became undetectable after a four-week washout period when CORT-treated adolescents exhibited improved reversal learning. Together, these findings demonstrate that chronic CORT exposure at the dose of 5 mg/kg endows adolescent individuals with enhanced cognitive capacities, possibly supported by increased hippocampal neuroplasticity. This study also highlights mild elevation of CORT levels during adolescence as a potential approach of promoting adaptive behaviors.