Beneficial effects of enriched environment on adolescent rats from stressed pregnancies

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Abstract
The capacity of an early environmental intervention to normalize the behavioural and immunological dysfunctions produced by a stressed pregnancy was investigated. Pregnant Sprague‐Dawley rats underwent three 45‐min sessions per day of prenatal restraint stress (PS) on gestation days 11–21, and their offspring were assigned to either an enriched‐environment or standard living cages throughout adolescence [postnatal days (pnd) 22–43]. Juvenile rats from stressed pregnancies had a prominent depression of affiliative/playful behaviour and of basal circulating CD4 T lymphocytes, CD8 T lymphocytes and T4/T8 ratio. They also showed increased emotionality and spleen and brain frontal cortex levels of pro‐inflammatory interleoukin‐1β (IL‐1β) cytokine. A more marked response to cyclophosphamide (CPA: two 2 mg/kg IP injections) induced immunosuppression was also found in prenatal stressed rats. Enriched housing increased the amount of time adolescent PS rats spent in positive species‐typical behaviours (i.e. play behaviour), reduced emotionality and reverted most of immunological alterations. In addition to its effects in PS rats, enriched housing increased anti‐inflammatory IL‐2 and reduced pro‐inflammatory IL‐1β production by activated splenocytes, also producing a marked alleviation of CPA‐induced immune depression. In the brain, enriched housing increased IL‐1β values in hypothalamus, while slightly normalizing these values in the frontal cortex from PS rats. This is a first indication that an environmental intervention, such as enriched housing, during adolescence can beneficially affect basal immune parameters and rats response to both early stress and drug‐induced immunosuppression.