title: Prenatal corticosteroid exposure alters early developmental seizures and behavior.
abstract: In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2×10mg/kg), betamethasone (2×0.4mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species.
authors.affiliation: Department of Cell Biology & Anatomy, Department of Pediatrics, New York Medical College, 15 Dana Rd., Valhalla, NY, USA. Libor Velisek@nymc.edu
authors.forename: Libor
authors.initials: L
authors.lastname: Velíšek
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001623:Betamethasone / Q000008:administration & dosage / Q000633:toxicity*; D002191:Canrenoic Acid / Q000494:pharmacology / Q000633:toxicity; D003292:Convulsants / Q000633:toxicity; D004198:Disease Susceptibility / Q000139:chemically induced; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D005481:Flurothyl / Q000633:toxicity; D006854:Hydrocortisone / Q000008:administration & dosage / Q000633:toxicity*; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D000451:Mineralocorticoid Receptor Antagonists; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012640:Seizures / Q000139:chemically induced*; D013226:Status Epilepticus / Q000139:chemically induced; D015430:Weight Gain / Q000187:drug effects
chemical_list: D003292:Convulsants; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D002191:Canrenoic Acid; D001623:Betamethasone; D005481:Flurothyl; D007608:Kainic Acid; D006854:Hydrocortisone