Abstract
Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. While adolescent individuals show heightened stress-induced hormonal responses compared to adults, it is unclear whether and how the behavioral and neurobiological consequences of chronic stress would differ between the two age groups. Here we address this issue by examining the effects of chronic exposure to the stress hormone, corticosterone (CORT), in both adolescent and adult animals. Male Sprague-Dawley (SD) rats were injected intraperitoneally with CORT (40 mg/kg) or vehicle for 21 days during adolescence (post-natal day (PND) 29–49) or adulthood (PND 71–91) and then subjected to behavioral testing or sacrifice for western blot analyses. Despite of similar physical and neuroendocrine effects in both age groups, chronic CORT treatment produced a series of behavioral and neurobiological effects with striking age differences. While CORT-treated adult animals exhibited decreased sucrose preference, increased anxiety levels and cognitive impairment, CORT-treated adolescent animals demonstrated increased sucrose preference, decreased anxiety levels, and increased sensorimotor gating functions. These differential behavioral alterations were accompanied by opposite changes in the two age groups in the expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylation of the obligatory subunit of the NMDA receptor, GluN1, and PSD-95 in rat hippocampus. These results suggest that prolonged glucocorticoid exposure during adolescence produces different behavioral and neurobiological effects from those in adulthood, which may be due to the complex interaction between glucocorticoids and the ongoing neurodevelopmental processes during this period.
Highlights
Stressful life events constitute one of the environmental risk factors of several psychiatric disorders, such as depression, anxiety and schizophrenia (Hammen, 2005; Varese et al, 2012)
We investigated the potential changes in expression levels of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptors in rat hippocampus following chronic CORT treatment in both age groups
We found no alterations of precursor of BDNF (proBDNF) in either age group following chronic CORT treatment (Ps > 0.63)
Summary
Stressful life events constitute one of the environmental risk factors of several psychiatric disorders, such as depression, anxiety and schizophrenia (Hammen, 2005; Varese et al, 2012). One developmental stage that is of particular interest in this study regards adolescence, a critical window witnessing the typical onset of many psychiatric disorders (O’Donnell, 2011) and the continued maturation of stress systems (Romeo, 2013). It has been well-established that compared to adults, adolescent animals exhibited different hypothalamo-pituitary-adrenal (HPA) axis functions in that they showed prolonged exposure to stress hormones, including adrenocorticotropic hormone (ACTH) and corticosterone (CORT), in response to both acute and chronic stress (Romeo, 2013). The behavioral and neurobiological consequences following the increased hormonal stress responses, still await systematic evaluation
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