Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat.
Until recently, the synthetic glucocorticoid dexamethasone was commonly used to lessen the morbidity of chronic lung disease in premature infants. This practice diminished as dexamethasone use was linked to an increased incidence of cerebral palsy and short-term neurodevelopmental delay. Of more concern is the fact that we know little regarding dexamethasone effects on long-term neurodevelopment. To study the effects of neonatal dexamethasone exposure on long-term neurodevelopment, we have developed a rat model where newborn pups are exposed to tapering doses of dexamethasone at time points corresponding to the neurodevelopmental age when human infants are traditionally exposed to this drug in the neonatal intensive care unit. Using a within-litter design, pups were assigned to one of three groups on postnatal day 2 (P2): handled controls, saline-injected controls, and animals receiving intramuscular dexamethasone between P3 and P6. Somatic growth was decreased in dexamethasone-treated animals. Dexamethasone-treated animals demonstrated slight delays in indexes of neurodevelopment and physical maturation at P7 and P14, but not P20. In adolescence (P45), there was no difference between groups in an open field test. However, as adult dexamethasone-treated animals were less active in the open field and spent more time in closed arms of the elevated plus maze. The serum corticosterone response to crowding stress in dexamethasone-treated animals was no different from controls, but they demonstrate a delay in return of corticosterone levels to baseline. These differences in behavior and hormonal stress responsiveness suggest that neonatal dexamethasone exposure may permanently alter function of the neuroendocrine stress axis.
Neal
Charles R
CR
Mental Health Research Institute and Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0720, USA. crnj@umich.edu
Weidemann
Gabrielle
G
Kabbaj
Mohamed
M
Vázquez
Delia M
DM
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development*; D003441:Crowding / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D023421:Models, Animal; D009929:Organ Size; D010913:Pituitary-Adrenal System / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism
D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone