Beneficial effects of enriched environment on adolescent rats from stressed pregnancies.
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.
Laviola
Giovanni
G
Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Viale Regina Elena, 299, I-00161 Roma, Italy. laviola@iss.it
Rea
Monica
M
Morley-Fletcher
Sara
S
Di Carlo
Simonetta
S
Bacosi
Antonella
A
De Simone
Roberta
R
Bertini
Mario
M
Pacifici
Roberta
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000276:immunology; D001923:Brain Chemistry; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003520:Cyclophosphamide / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D004780:Environment, Controlled; D005106:Exploratory Behavior; D005260:Female; D007166:Immunosuppressive Agents / Q000633:toxicity; D007398:Interpersonal Relations; D007958:Leukocyte Count; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology / Q000628:therapy*
D016207:Cytokines; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D003345:Corticosterone