Neonatal exposure to estradiol in rats influences neuroactive steroid concentrations, GABAA receptor expression, and behavioral sensitivity to anxiolytic drugs
Article first published online: 24 MAR 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 113, Issue 5, pages 1285–1295, June 2010
How to Cite
Calza, A., Sogliano, C., Santoru, F., Marra, C., Angioni, M. M., Mostallino, M. C., Biggio, G. and Concas, A. (2010), Neonatal exposure to estradiol in rats influences neuroactive steroid concentrations, GABAA receptor expression, and behavioral sensitivity to anxiolytic drugs. Journal of Neurochemistry, 113: 1285–1295. doi: 10.1111/j.1471-4159.2010.06696.x
- Issue published online: 4 MAY 2010
- Article first published online: 24 MAR 2010
- Received December 16, 2009; revised manuscript received March 10, 2010; accepted March 16, 2010.
- cerebral cortex;
- GABAA receptor;
- neuroactive steroid
J. Neurochem. (2010) 113, 1285–1295.
Gonadal steroids, in particular estradiol, exert important actions during pre- and perinatal periods in the regulation of sexual dimorphism and development of the nervous system. We have now examined the effects of neonatal estradiol administration in female rats on brain concentrations of the neuroactive steroids allopregnanolone and tetrahydrodeoxycorticosterone, expression of GABAA receptor subunits, and behavioral sensitivity to benzodiazepines and allopregnanolone. Administration of β-estradiol 3-benzoate on the day of birth resulted in marked decreases in the concentrations of progesterone and allopregnanolone in the cerebral cortex at 21, 60, and 180 days after birth. The concentrations of tetrahydrodeoxycorticosterone, 17β-estradiol, and dehydroepiandrosterone in the brain at 60 days were not affected by such treatment. Neonatal administration of β-estradiol 3-benzoate also increased the cerebrocortical abundance of α1, α2, and γ2 subunits of the GABAA receptor without affecting that of α3, α4, α5, or δ subunits. Diazepam induced a greater reduction in locomotor activity as well as a more pronounced anxiolytic-like effect in the elevated plus-maze test in rats subjected to neonatal treatment with β-estradiol 3-benzoate than in vehicle-treated controls, while allopregnanolone induced a similar effect in both groups. These effects of estradiol suggest that it plays a major role in regulation both of GABAergic transmission and of the abundance of endogenous modulators of such transmission during development of the central nervous system.