Role of allopregnanolone in regulation of GABA A receptor plasticity during long-term exposure to and withdrawal from progesterone

Role of allopregnanolone in regulation of GABA A receptor plasticity during long-term exposure to... Here we summarize recent data from our laboratory pertaining to the effects of fluctuations in the brain concentrations of the progesterone (PROG) metabolite allopregnanolone (3α,5α-TH PROG) on the expression and function of γ-aminobutyric acid type A (GABA A ) receptors. The effects of long-term exposure to progesterone and of its sudden withdrawal on the activity of GABA A receptors and on the abundance of receptor subunit mRNAs were examined in cultured rat cerebellar granule cells and cortical neurons. The effects of a persistent reduction in the brain concentration of 3α,5α-TH PROG on GABA A receptor function and gene expression were examined in vivo in rats subjected to long-term administration of oral contraceptives. Our results demonstrate that long-lasting changes in the exposure of GABA A receptors to this PROG metabolite induce marked effects on receptor structure and function. These effects of 3α,5α-TH PROG appear to be mediated through modulation of GABA A receptor signaling mechanisms that control the expression of specific receptor subunit genes. Furthermore, the specific outcomes of such signaling appear to differ among neurons derived from different regions of the brain. Neuroactive steroids such as 3α,5α-TH PROG might thus exert differential actions on GABA A receptor plasticity in distinct neuronal cell populations, likely accounting for some of the physiological effects induced by these compounds. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Reviews Elsevier

Role of allopregnanolone in regulation of GABA A receptor plasticity during long-term exposure to and withdrawal from progesterone

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Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science B.V.
ISSN
0165-0173
DOI
10.1016/S0165-0173(01)00125-4
Publisher site
See Article on Publisher Site

Abstract

Here we summarize recent data from our laboratory pertaining to the effects of fluctuations in the brain concentrations of the progesterone (PROG) metabolite allopregnanolone (3α,5α-TH PROG) on the expression and function of γ-aminobutyric acid type A (GABA A ) receptors. The effects of long-term exposure to progesterone and of its sudden withdrawal on the activity of GABA A receptors and on the abundance of receptor subunit mRNAs were examined in cultured rat cerebellar granule cells and cortical neurons. The effects of a persistent reduction in the brain concentration of 3α,5α-TH PROG on GABA A receptor function and gene expression were examined in vivo in rats subjected to long-term administration of oral contraceptives. Our results demonstrate that long-lasting changes in the exposure of GABA A receptors to this PROG metabolite induce marked effects on receptor structure and function. These effects of 3α,5α-TH PROG appear to be mediated through modulation of GABA A receptor signaling mechanisms that control the expression of specific receptor subunit genes. Furthermore, the specific outcomes of such signaling appear to differ among neurons derived from different regions of the brain. Neuroactive steroids such as 3α,5α-TH PROG might thus exert differential actions on GABA A receptor plasticity in distinct neuronal cell populations, likely accounting for some of the physiological effects induced by these compounds.

Journal

Brain Research ReviewsElsevier

Published: Nov 1, 2001

References

  • The effects of inhibitors of GABAergic transmission and stress on brain and plasma allopregnanolone concentrations
    Barbaccia, M.L; Roscetti, G; Trabucchi, M; Purdy, R; Mostallino, M.C; Concas, A; Biggio, G
  • Binding of ( 3 H)DMCM, a convulsive benzodiazepine ligand, to rat brain membranes: preliminary studies
    Breastrup, C; Nielsen, M; Honoré, T
  • Evaluation of in vivo interactions in mice between flurazepam and two neuroactive steroids
    Deutsch, S.I; Rosse, R.B; Steinberg, K; Morn, C; Koetzner, L; Riggs, R; Mastropaolo, J
  • Molecular and functional adaptation of the GABA A receptor complex during pregnancy and after delivery in the rat brain
    Follesa, P; Floris, S; Tuligi, G; Mostallino, M.C; Concas, A; Biggio, G
  • Anti-anxiety effects of progesterone and some of its reduced metabolites: an evaluation using the burying behavior test
    Picazo, O; Fernández-Guasti, A

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