The effects of adolescent stress and minocycline treatment on adult anxiety-related behavior in male and female Sprague Dawley rats

During early developmental stages, such as adolescence, the brain is sensitive to experiences that continuously shape future behavior, cognition, neural plasticity, and neuroimmune function. Particularly, chronic psychological stress during adolescence significantly heightens the risk of developing abnormal behaviors and a range of psychiatric disorders in adulthood, such as anxiety, depression, and schizophrenia. The neural mechanisms behind the etiology of these disorders are not yet fully understood, although emerging evidence suggests that the neuroimmune system may play a role in this development and also offer a potential target for therapeutic intervention. The current study explored the extent to which neuroimmune responses modulate the effects of adolescent stress on anxiety-related behavior in adulthood. Male and female Sprague Dawley rats were subjected to chronic variable psychological stressors during adolescence in the presence or absence of minocycline in their drinking water. In adulthood (postnatal days 83, 86-89), behavioral testing was performed to assess anxiety-like behaviors using the elevated zero maze (EZM) and the open field test (OFT). Anxiety-like behaviors varied across sex, stress condition, behavioral tests, and minocycline treatment. Adult females displayed decreased anxiety-like behavior in the EZM relative to males, independent of adolescent stress or minocycline treatment, while males exhibited lower levels of anxiety in the OFT than females. Contrary to expectations, adolescent stress reduced anxiety in the OFT overall. Interestingly, minocycline increased anxiety in non-stressed males, suggesting that a reduction in microglial activity during adolescence alters the development of neural networks underlying anxiety in males. These data suggest that adolescent stress and minocycline exert complex and sex-specific effects on anxiety-related behaviors, highlighting the complexity of stress and neuroimmune interactions in shaping adult behavioral outcomes.