Beneficial effects of enriched environment on adolescent rats from stressed pregnancies

Eur J Neurosci. 2004 Sep;20(6):1655-64. doi: 10.1111/j.1460-9568.2004.03597.x.


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-1beta (IL-1beta) 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-1beta production by activated splenocytes, also producing a marked alleviation of CPA-induced immune depression. In the brain, enriched housing increased IL-1beta 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Brain / drug effects
  • Brain / immunology
  • Brain Chemistry
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Corticosterone / blood
  • Cyclophosphamide / toxicity
  • Cytokines / metabolism
  • Environment, Controlled*
  • Exploratory Behavior
  • Female
  • Immunosuppressive Agents / toxicity
  • Interpersonal Relations
  • Leukocyte Count
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical
  • Stress, Physiological / blood
  • Stress, Physiological / physiopathology
  • Stress, Physiological / therapy*


  • Cytokines
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Corticosterone