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  Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology

Rupprecht, R., di Michele, F., Hermann, B., Ströhle, A., Lancel, M., Romeo, E., et al. (2001). Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology. Brain Research Reviews, 37(1-3 Sp. Iss. SI), 59-67.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A2E2-B Version Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A2E3-9
Genre: Journal Article
Alternative Title : Brain Res. Rev.

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 Creators:
Rupprecht, R1, Author
di Michele, F1, Author
Hermann, B1, Author
Ströhle, A1, Author
Lancel, M1, Author
Romeo, E1, Author
Holsboer, F1, Author
Affiliations:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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Free keywords: neurosteroid; neuroactive steroid; ligand-gated ion channel; depression; anxiety
 Abstract: Besides their binding to cognate intracellular receptors gonadal steroids may also act as functional antagonists at the 5-HT3 receptor. A structure-activity relationship for the actions of a variety of steroids at the 5-HT3 receptor was elaborated that differed considerably from that known for GABA(A) receptors. Steroids appear to interact allosterically with ligand-gated ion channels at the receptor membrane interface. The functional antagonism of gonadal steroids at the 5-HT3 receptor may play a role for the development and course of nausea during pregnancy and of psychiatric disorders. Moreover, we could demonstrate that 3alpha-reduced neuroactive steroids concurrently modulate the GABA(A) receptor and regulate gene expression via the progesterone receptor after intracellular oxidation. Animal studies showed that progesterone is converted rapidly into GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity in a dose dependent fashion in male Wister rats. Moreover, progesterone and 3alpha,5alpha-tetrahydroprogesterone produce a benzodiazepine-like sleep EEG profile in rats and humans. In addition, there is a dysequilibrium of such 3alpha-reduced neuroactive steroids during major depression which is corrected by successful treatment with antidepressants. Neuroactive steroids may further be involved in the treatment of depression and anxiety with antidepressants in patients during ethanol withdrawal. First studies in patients with panic disorder suggest that neuroactive steroids may also play a pivotal role in human anxiety. The genomic and non-genomic effects of steroids in the brain contribute to the pathophysiology of psychiatric disorders and the mechanisms of action of antidepressants. Neuroactive steroids affect a broad spectrum of behavioral functions through their unique molecular properties and may constitute a yet unexploited class of drugs. (C) 2001 Elsevier Science BY All rights reserve

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Language(s): eng - English
 Dates: 2001-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 4207
ISI: 000173120500006
 Degree: -

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Title: Brain Research Reviews
  Alternative Title : Brain Res. Rev.
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 37 (1-3 Sp. Iss. SI) Sequence Number: - Start / End Page: 59 - 67 Identifier: ISSN: 0165-0173