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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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Datensatz-Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A2E2-B Versions-Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A2E3-9
Genre: Zeitschriftenartikel
Alternativer Titel : Brain Res. Rev.

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

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Schlagwörter: neurosteroid; neuroactive steroid; ligand-gated ion channel; depression; anxiety
 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2001-11
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 4207
ISI: 000173120500006
 Art des Abschluß: -

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Titel: Brain Research Reviews
  Alternativer Titel : Brain Res. Rev.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 37 (1-3 Sp. Iss. SI) Artikelnummer: - Start- / Endseite: 59 - 67 Identifikator: ISSN: 0165-0173