Dexamethasone exposure during the neonatal period alters ORL1 mRNA expression in the hypothalamic paraventricular nucleus and hippocampus of the adult rat.
Dexamethasone is commonly used to limit the severity of chronic lung disease in premature infants with severe respiratory distress syndrome. Recent literature has demonstrated an association between dexamethasone exposure in critically ill premature neonates and later development of cerebral palsy. However, the majority of children exposed to dexamethasone in the neonatal period do not develop cerebral palsy or global developmental delay, and other more subtle effects of early life glucocorticoid exposure may go unnoticed. Presently, little is known regarding possible effects of early dexamethasone exposure on development of neuropeptide systems that are sensitive to glucocorticoid modulation. One such system is the pain-related opioid system that interacts with the stress-related limbic-hypothalamic pituitary adrenal (LHPA) axis. In the present study, a neonatal rat model was used to expose newborn rats to dexamethasone. Using a within-litter design, on postnatal days P3 through P6, pups were either handled, or they received a daily intramuscular injection of saline or dexamethasone. Adult animals were sacrificed on day of life P120, their brains were removed and quick-frozen. Using in situ hybridization histochemistry, mRNA expression of the opioid receptor-like (ORL1) receptor was measured in the paraventricular nucleus of the hypothalamus (PVN) and the hippocampal formation. In dexamethasone-treated adult male rats, ORL1 mRNA expression was increased in the PVN and dentate gyrus, but decreased in area CA1, when compared to handled and vehicle controls. These results suggest that prolonged glucocorticoid receptor (GR) occupation in the neonatal period leads to permanent alterations in ORL1 expression in the LHPA stress axis of the adult rat.
Neal
Charles R
CR
Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109-0720, USA. crnj@umich.edu
VanderBeek
Brian L
BL
Vázquez
Delia M
DM
Watson
Stanley J
SJ
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D000094942:Nociceptin Receptor
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat