NEONATAL TREATMENT OF RATS WITH THE NEUROACTIVE STEROID TETRAHYDRODEOXYCORTICOSTERONE (THDOC) ABOLISHES THE BEHAVIORAL AND NEUROENDOCRINE CONSEQUENCES OF ADVERSE EARLY-LIFE EVENTS
Vk. Patchev et al., NEONATAL TREATMENT OF RATS WITH THE NEUROACTIVE STEROID TETRAHYDRODEOXYCORTICOSTERONE (THDOC) ABOLISHES THE BEHAVIORAL AND NEUROENDOCRINE CONSEQUENCES OF ADVERSE EARLY-LIFE EVENTS, The Journal of clinical investigation, 99(5), 1997, pp. 962-966
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.