Beneficial Effects of Physical Activity and Crocin Against Adolescent Stress Induced Anxiety or Depressive-Like Symptoms and Dendritic Morphology Remodeling in Prefrontal Cortex in Adult Male Rats

Increasing evidence suggests that exposure to chronic stress during adolescent period may lead to behavioral and neuronal morphology deficits in adulthood. This study examined whether crocin, the main active saffron constituent, and voluntary exercise, alone or combined, could prevent the detrimental influences of chronic restraint stress during adolescent (postnatal days, PND, 30-40) on behavioral and morphological deficits in adult (PND60) male rats. Results showed that plasma corticosterone levels increased at PND40, but not PND60 in stressed rats. Moreover, stressed rats demonstrated enhanced anxiety levels and depression like behaviors in adulthood. These behavioral abnormalities were accompanied by a decline in apical dendritic length in both infralimbic and prelimbic regions and dendritic branches in infralimbic region of the prefrontal cortex. Treatment with crocin, exposure to wheel running activity, and the combined interventions alleviated both behavioral and morphological deficits induced by adolescent stress. Moreover, these treatments exerted positive neuronal morphological effects in the prefrontal cortex in non-stressed animals. Our findings provide important evidences that exercise as a non-pharmacological intervention and crocin treatment during pre-pubertal period can protect against adolescent stress induced behavioral and morphological abnormalities in adulthood.