Effects of perinatal oxycodone exposure on the response to CRH in late adolescent rats.
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.
Sithisarn
Thitinart
T
Department of Pediatrics, Chandler Medical Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA.
Bada
Henrietta S
HS
Dai
Hongying
H
Reinhardt
Christopher R
CR
Randall
David C
DC
Legan
Sandra J
SJ
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000254:growth & development*; D008098:Litter Size / Q000187:drug effects; D008297:Male; D010098:Oxycodone / Q000633:toxicity*; D036801:Parturition / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
D000701:Analgesics, Opioid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D010098:Oxycodone; D006854:Hydrocortisone