NEONATAL TREATMENT OF RATS WITH THE NEUROACTIVE STEROID TETRAHYDRODEOXYCORTICOSTERONE (THDOC) ABOLISHES THE BEHAVIORAL AND NEUROENDOCRINE CONSEQUENCES OF ADVERSE EARLY-LIFE EVENTS

Stressful experience during early brain development has been shown to produce profound alterations in several mechanisms of adaptation, whil e several signs of behavioral and neuroendocrine impairment resulting from neonatal exposure to stress resemble symptoms of dysregulation as sociated with major depression. This study demonstrates that when appl ied concomitantly with the stressful challenge, the steroid GABA(A) re ceptor agonist 3,21-dihydropregnan-20-one (tetrahydrodeoxycorticostero ne, THDOC) can attenuate the behavioral and neuroendocrine consequence s of repeated maternal separation during early life, e.g., increased a nxiety, an exaggerated adrenocortical secretory response to stress, im paired responsiveness to glucocorticoid feed-back, and altered transcr iption of the genes encoding corticotropin-releasing hormone (CRH) in the hypothalamus and glucocorticoid receptors in the hippocampus. Thes e data indicate that neuroactive steroid derivatives with GABA-agonist ic properties may exert persisting stress-protective effects in the de veloping brain, and may form the basis for therapeutic agents which ha ve the potential to prevent mental disorders resulting from adverse ex perience during neonatal life.