Induction of a hyperanxious state by antenatal dexamethasone: a case for less detrimental natural corticosteroids

Biol Psychiatry. 2006 May 1;59(9):844-52. doi: 10.1016/j.biopsych.2005.08.020. Epub 2005 Sep 28.

Abstract

Background: Synthetic glucocorticoids are commonly prescribed during pregnancy, despite a lack of systematic investigations of their potential impact on the developing brain and neurological and behavioral performance.

Methods: Neuroendocrine parameters and behavior in the adult offspring of pregnant Wistar rats treated antenatally with either dexamethasone (DEX) or corticosterone (CORT) were monitored; DEX (.1 mg/kg and 1 mg/kg) and CORT (25 mg/kg) were given to pregnant rat dams on gestation days 18 and 19.

Results: Despite normal basal levels of corticosterone, the adult offspring of mothers given DEX or CORT displayed abnormal responses in the dexamethasone-suppression test. Neither treatment influenced spatial memory performance, but both DEX and CORT facilitated development of depression-like behavior following chronic stress. The latter finding demonstrates that high-dose antenatal corticotherapy can impair the organism's resilience to stress in adulthood. Interestingly, comparison of the progeny of CORT-treated and DEX-treated mothers revealed that the latter were more anxious.

Conclusions: Since DEX and CORT differ in their affinity for glucocorticoid and mineralocorticoid receptors and corticosteroid-binding globulin, our findings emphasize the need to consider the pharmacologic properties of antenatal corticotherapies and demonstrate the potential long-term benefits of ligands that can bind to both receptors.

Publication types

  • Comparative Study

MeSH terms

  • Adrenal Cortex Hormones / blood
  • Adrenal Cortex Hormones / toxicity*
  • Age Factors
  • Animals
  • Anxiety Disorders / blood
  • Anxiety Disorders / chemically induced*
  • Behavior, Animal
  • Birth Weight / drug effects
  • Depression / chemically induced
  • Dexamethasone / blood
  • Dexamethasone / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Female
  • Freezing Reaction, Cataleptic / drug effects
  • Helplessness, Learned
  • Hypothalamo-Hypophyseal System / drug effects
  • Male
  • Maternal Deprivation
  • Memory / drug effects
  • Pituitary-Adrenal System / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Wistar
  • Sex Factors
  • Spatial Behavior / drug effects

Substances

  • Adrenal Cortex Hormones
  • Dexamethasone