Effects of tapering neonatal dexamethasone on rat growth, neurodevelopment, and stress response.
Dexamethasone is commonly used to lessen the morbidity of chronic lung disease in premature infants, but little is known regarding neurological consequences of its prolonged use. To study neurological effects of dexamethasone, we have developed a rat model in which newborn pups are exposed to tapering doses of dexamethasone at a time corresponding neurodevelopmentally to human exposure in the neonatal intensive care unit. On postnatal day (PD) 2, litters were divided into three groups: 1) handled controls, 2) saline-injected animals, and 3) animals injected with tapering doses of intramuscular dexamethasone between PD 3 and 6. Somatic growth and brain weight were decreased in dexamethasone-treated animals. Dexamethasone-treated animals demonstrated delays in gross neurological development on PD 7 and 14 but not PD 20. In late adolescence (PD 33), dexamethasone-treated animals were less active in light and dark environments, while demonstrating a blunted serum corticosterone response to a novel stress. The dissociation between behavioral and hormonal stress responsiveness suggests that neonatal dexamethasone exposure permanently alters central nervous system function, particularly within the neuroendocrine stress axis. This may lead to increased risk for learning impairment and maladaptive responses to the environment.
Flagel
Shelly B
SB
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109-0720, USA.
Vázquez
Delia M
DM
Watson
Stanley J
SJ
Neal
Charles R
CR
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000254:growth & development*; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000031:analogs & derivatives; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D015931:Intensive Care, Neonatal; D008297:Male; D009460:Neurologic Examination; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*
D005938:Glucocorticoids; D003907:Dexamethasone; D011464:Epoprostenol; C427248:treprostinil; D003345:Corticosterone