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  Mechanisms underlying the protective potential of alpha- tocopherol (vitamin E) against haloperidol-associated neurotoxicity

Post, A., Rücker, M., Ohl, F., Uhr, M., Holsboer, F., Almeida, O., et al. (2002). Mechanisms underlying the protective potential of alpha- tocopherol (vitamin E) against haloperidol-associated neurotoxicity. Neuropsychopharmacology, 26(3), 397-407.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A243-2 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A244-F
Genre: Journal Article
Alternative Title : Neuropsychopharmacology

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 Creators:
Post, A1, Author
Rücker, M1, Author
Ohl, F1, Author
Uhr, M1, Author
Holsboer, F1, Author
Almeida, OFX1, Author
Michaelidis, TM1, Author
Affiliations:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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Free keywords: haloperidol; NF-kappa B/I kappa-B; p53; apoptosis; Bax; tardive dyskinesia
 Abstract: The undesired side-effects of haloperidol treatment include a number of extrapyramidal side-effects which have been proposed to result from drug-induced damage to the basal ganglia. The drug also causes irregular movements and locomotor patterns in experimental animals. Here we show that haloperidol treatment in rats is associated with increases in the expression of 1753 and the ratio of pro-apoptotic (Bax) to anti-apoptotic (Bcl- 2/Bcl-x(1)) proteins in the hippocampus and caudate putamen (CPu). In addition, haloperidol induces the DNA binding activity of the redox-sensitive nuclear factor-kappa B (NF- kappaB) and concomitantly upregulates the levels of the phosphorylated form of IkappaBalpha protein in vivo. Similar responses are observed when a mouse hippocampal cell line (HT- 22) is treated with haloperidol and/or vitamin E. Interestingly, all of these biochemical effects of haloperidol arc significantly attenuated when animals or cultured cells are pretreated with a-tocopherol (vitamin E). Consistent with this, vitamin E is demonstrated to substantially reduce the haloperidol-induced impairment of locomotor activity in rats. Collectively, the data indicate the usefulness of vitamin E as an adjunct to haloperidol treatment and provide initial clues about the underlying molecular mechanisms involved in these effects. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science In

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Language(s): eng - English
 Dates: 2002-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 4197
ISI: 000173976300013
 Degree: -

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Title: Neuropsychopharmacology
  Alternative Title : Neuropsychopharmacology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 26 (3) Sequence Number: - Start / End Page: 397 - 407 Identifier: ISSN: 0893-133X