Format

Send to

Choose Destination
J Clin Invest. 1997 Mar 1;99(5):962-6.

Neonatal treatment of rats with the neuroactive steroid tetrahydrodeoxycorticosterone (THDOC) abolishes the behavioral and neuroendocrine consequences of adverse early life events.

Author information

1
Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.

Abstract

Stressful experience during early brain development has been shown to produce profound alterations in several mechanisms of adaptation, while several signs of behavioral and neuroendocrine impairment resulting from neonatal exposure to stress resemble symptoms of dysregulation associated with major depression. This study demonstrates that when applied concomitantly with the stressful challenge, the steroid GABA(A) receptor agonist 3,21-dihydropregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) can attenuate the behavioral and neuroendocrine consequences of repeated maternal separation during early life, e.g., increased anxiety, an exaggerated adrenocortical secretory response to stress, impaired responsiveness to glucocorticoid feedback, and altered transcription of the genes encoding corticotropin-releasing hormone (CRH) in the hypothalamus and glucocorticoid receptors in the hippocampus. These data indicate that neuroactive steroid derivatives with GABA-agonistic properties may exert persisting stress-protective effects in the developing brain, and may form the basis for therapeutic agents which have the potential to prevent mental disorders resulting from adverse experience during neonatal life.

PMID:
9062354
PMCID:
PMC507904
DOI:
10.1172/JCI119261
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center