de.mpg.escidoc.pubman.appbase.FacesBean
English
 
Help Guide Disclaimer Contact us Login
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

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

MPS-Authors

Post,  A
Max Planck Institute of Psychiatry, Max Planck Society;

Rücker,  M
Max Planck Institute of Psychiatry, Max Planck Society;

Ohl,  F
Max Planck Institute of Psychiatry, Max Planck Society;

Uhr,  M
Max Planck Institute of Psychiatry, Max Planck Society;

Holsboer,  F
Max Planck Institute of Psychiatry, Max Planck Society;

Almeida,  OFX
Max Planck Institute of Psychiatry, Max Planck Society;

Michaelidis,  TM
Max Planck Institute of Psychiatry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)
There are no public fulltexts available
Supplementary Material (public)
There is no public supplementary material available
Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-A243-2
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