Abstract |
The therapeutic management of methamphetamine (METH)-induced psychoses often involves treatment with the typical antipsychotic drug and dopamine D2 receptor antagonist haloperidol. We report here that subchronic haloperidol administration after a high-dose regimen of METH produces a heretofore unrecognized toxicity to GABAergic cells, as reflected by GAD67 mRNA expression histochemistry, in the rat substantia nigra pars reticulata (SNr) through an acute and persistent augmentation of glutamate release, NMDA receptor activation, and DNA fragmentation. The dopaminergic cells in the substantia nigra pars compacta were unaffected by METH or haloperidol alone or the combination of METH and haloperidol. These findings suggest that the current therapeutic management of METH-induced psychoses with haloperidol may be contraindicated because of a resultant GABAergic cell death in the SNr, which may predispose some individuals to the development of hyperkinetic movement disorders and seizures.
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Authors | Theo Hatzipetros, Jamie G Raudensky, Jean-Jacques Soghomonian, Bryan K Yamamoto |
Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience
(J Neurosci)
Vol. 27
Issue 22
Pg. 5895-902
(May 30 2007)
ISSN: 1529-2401 [Electronic] United States |
PMID | 17537960
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dopamine D2 Receptor Antagonists
- Receptors, Dopamine D2
- Glutamic Acid
- Methamphetamine
- gamma-Aminobutyric Acid
- Haloperidol
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Topics |
- Animals
- Dopamine D2 Receptor Antagonists
- Dose-Response Relationship, Drug
- Glutamic Acid
(biosynthesis, metabolism)
- Haloperidol
(toxicity)
- Male
- Methamphetamine
(administration & dosage)
- Rats
- Rats, Sprague-Dawley
- Receptors, Dopamine D2
(physiology)
- Substantia Nigra
(cytology, drug effects)
- Time Factors
- gamma-Aminobutyric Acid
(physiology)
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