Early social deprivation does not affect cortisol response to acute and chronic stress in zebrafish

Social isolation is a well-established technique for inducing early adversity but, in rodent models, the need of parental care makes it difficult to distinguish the effects of social deprivation from the consequences of nutritional deficiencies. Zebrafish do not require parental care, allowing separation of social deprivation from nutritional deprivation, and have emerged as a promising model to study ontogeny of normal and pathological behaviors relevant for human neuropsychological disorders. Previous reports of life-long isolation in zebrafish showed some consistency with mammalian literature, depicting later social deficits and locomotor hyperactivity. However, unlike reports of higher anxiety and stress behavior in isolated rodents and primates, behavioral responses were tapered in isolated fish. To examine whether life-long developmental isolation has a dampening effect on zebrafish endocrine stress response, we applied stressors to zebrafish siblings that were either isolated or socialized, and compared their whole-body cortisol levels with non-stressed control siblings kept in low-housing densities. Utilizing previously-validated paradigms (exposure to novel tank and unpredictable chronic stress), we exposed separate groups (n = 9-14, mixed-sex) of social and isolated zebrafish to acute and chronic stressors and measured their cortisol levels. A univariate ANOVA and post-hoc Tukey's HSD tests confirmed that compared to socially raised control fish, developmental isolation did not increase baseline cortisol levels in zebrafish. Additionally, compared to the non-stressed condition, application of both acute and chronic stressors significantly increased cortisol levels in isolated fish and, to a similar degree, to socially raised fish. Our findings suggest that zebrafish isolation studies may help separate effects of social deprivation from non-social aspects of early adversity. These studies further substantiate the use of developmental isolation in zebrafish, particularly with acute and chronic stress paradigms, for modeling neuropsychological disorders.Lay Summary: A difficult childhood can make humans react more frequently or severely to later stress and modeling this effect in animals can help explain how and why early stress affects subsequent mental and physical health. Early social isolation does not affect later response to stressful situations in adult zebrafish, providing us with a model of psychiatric disorders that allows separation of effects of poor physical environments (lacking food, shelter, etc.) from poor social environments (lack of appropriate socialization).