Abstract
For years, it has been known that neuroleptics have the capacity to interfere with the mitochondrial respiratory chain in vitro. We report that haloperidol and fluphenazine, classical neuroleptics, cause a generalized reduction in the activity of NADH:ubiquinone oxidoreductase (complex I) in the rat brain in vivo, an effect that was not observed with the atypical neuroleptic, clozapine. MPTP, which bears significant structural similarities with haloperidol, also demonstrated a significant reduction in complex I activity after low-dose, chronic administration. Interestingly, an increase in the activity of cytochrome-c oxidase (complex IV), probably reflecting enhanced functional neuronal activity, was observed in the frontal cortex of all chronically treated animals, an effect that is unlikely to result from compensation for the inhibition of complex I. Results suggest that previous findings, in which a reduction in the activity of cytochrome-c oxidase was observed in postmortem brain samples from schizophrenics, are not dependent on treatment with neuroleptics.
Footnotes
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Send reprint requests to: Professor Lars Oreland, Department of Medical Pharmacology, University of Uppsala, Box 593, 751 24, Uppsala, Sweden.
- Abbreviations:
- COX
- cytochrome-c oxidase (complex IV)
- HPP+
- haloperidol pyridinium derivative
- MAO
- monoamine oxidase
- MPTP
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- MPP+
- 1-methyl-4-phenylpyridinium
- complex I
- NADH:ubiquinone oxidoreductase
- ATP
- adenosine triphosphate
- Received April 12, 1996.
- Accepted September 12, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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