We hypothesized that prenatal oxycodone exposure suppresses the Hypothalamic-Pituitary-Adrenal (HPA) response to stress in late adolescence. Dark Agouti rats were given either intravenous oxycodone or vehicle (controls, CON) daily from gestation day 8 until postnatal day (PD) 5. At PD 45, the male and female offspring received intravenously either ovine corticotropin releasing hormone (CRH) or saline. Plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined before, and 15, 30, and 60 min after injection. Prenatal oxycodone had no effect on baseline ACTH values; CRH elicited a greater ACTH response than saline. In males, prenatal oxycodone delayed and enhanced the peak ACTH response to CRH, but had no effect in females. The CORT response to CRH was not different between oxycodone and CON; however mean CORT levels in females were significantly higher than those in males at baseline and after stimulation. These results demonstrate that prenatal oxycodone increases pituitary response to CRH in late adolescent male rats, but not in females. The absence of an enhanced adrenal response in oxycodone-exposed males suggests either desensitization or maximal adrenal response to a high CRH dose. The mechanisms of postnatal sex-specific HPA dysregulation following prenatal oxycodone remain to be elucidated.
|Number of pages||7|
|Journal||Neurotoxicology and Teratology|
|State||Published - Mar 2008|
Bibliographical noteFunding Information:
This study was funded by a grant from the Kentucky Children's Hospital Children's Miracle Network awarded to Sandra J. Legan, Ph.D. and an endowment from the Mary Florence Jones Professorship awarded to Henrietta S. Bada, M.D. Thitinart Sithisarn, M.D was a K30 Scholar (K30 HL04163). The ovine CRH was provided by The National Hormone and Peptide Program and A.F. Parlow, PhD.
- Adrenocorticotropic hormone
- Corticotropin releasing hormone
- Hypothalamic-pituitary-adrenal axis
- Prenatal oxycodone
ASJC Scopus subject areas
- Developmental Neuroscience
- Cellular and Molecular Neuroscience