Post-weaning environmental enrichment alters affective responses and interacts with behavioral testing to alter nNOS immunoreactivity

Challenging early life events can dramatically affect mental health and wellbeing. Childhood trauma and neglect can increase the risk for developing depressive, anxiety, and substance abuse disorders. Early maternal separation in rodents has been extensively studied and induces long-lasting alterations in affective and stress responses. However, other developmental periods (e.g., the pubertal period) comprise a critical window whereby social and environmental complexity can exert lasting changes on the brain and behavior. In this study, we tested whether early life environmental complexity impacts affective responses, aggressive behaviors, and expression of neuronal nitric oxide synthase (nNOS), the synthetic enzyme for nitric oxide, in adulthood. Mice were weaned into social+nonsocial enrichment, social only enrichment, or standard (isolated) laboratory environments and were tested in open field, elevated plus maze, forced swim, and resident-intruder aggression tests 60 days later. Social+nonsocial enrichment reduced locomotor behavior and anxiety-like responses in the open field and reduced depressive-like responses in the forced swim test. Social housing increased open arm exploration in the elevated plus maze. Both social+nonsocial enrichment and social housing only reduced aggressive behaviors compared with isolation. Social+nonsocial enrichment also increased body mass gain throughout the study. Finally, socially-housed mice had reduced corticosterone concentrations compared with social+nonsocial-enriched mice. Behavioral testing reduced nNOS-positive neurons in the basolateral amygdala and the ventral lateral septum, but not in the social+nonsocial-enriched mice, suggesting that environmental complexity may buffer the brain against some environmental perturbations.