Adolescent environmental challenges affect adult function in male and female Long Evans rats

Abstract

Stress in adolescence is a putative risk factor for developing mental illnesses such as schizophrenia and mood disorders. Symptoms for these illnesses first emerge in late adolescence and early adulthood, with both incidence and severity being sexually dimorphic. Animal models can shed light on the neurobiological underpinnings of these disorders by allowing one to explore the relationship between a risk factor such as stress, and development of symptoms. In the current work the role of adolescent stress is explored in the development of biomarkers that are associated with adolescent-onset illnesses using Long Evans rats. Repeated exposure to predator odour was combined with social isolation during adolescence to create a novel stressor model. The specific objectives of this study were to determine (i) if repeated predator odour exposure altered measures related to sensorimotor gating (measured as prepulse inhibition, PPI), startle, and emotionality, and (ii) whether social support affected the outcome of predator odour stress. Predator odour elicited immediate avoidance, which did not habituate with repeated exposures, suggesting a strong behavioural stress response. In contrast to past work, few significant long-term effects were observed in animals exposed to predator odour compared with ones exposed to a non-threatening odour. Unexpectedly, animals exposed to a no odour (control) condition displayed altered PPI, startle response, anxiety-related behaviour, and memory, compared to rats exposed to a non-threatening, control odour or a predator odour. Moreover, the no odour animals showed altered expression of dopamine D2R receptor protein in the medial prefrontal cortex. The outcomes for this group were remarkably similar to those seen in animals raised in social isolation, suggesting an underlying similarity in the neurobiological mechanisms associated with these experiences that likely can be traced to being raised in environments lacking adequate social and physical complexity. Sex differences were noted in PPI, startle response, tests of anxiety- and depression-like behaviour, memory, and levels of dopamine D2R receptors, although the sex of the animal did not interact with stressor treatment to affect these measures. In conclusion, results of the current work provide further evidence for the importance of the social and physical environment to normal development during adolescence, as well as the importance of being male versus female.