NEUROLEPTIC-INDUCED MITOCHONDRIAL ENZYME ALTERATIONS IN THE RAT-BRAIN

For years, it has been known that neuroleptics have the capacity to in terfere with the mitochondrial respiratory chain in vitro. We report t hat haloperidol and fluphenazine, classical neuroleptics, cause a gene ralized reduction in the activity of NADH: ubiquinone oxidoreductase ( complex I) in the rat brain in vivo, an effect that was not observed w ith the atypical neuroleptic, clozapine. MPTP, which bears significant structural similarities with haloperidol, also demonstrated a signifi cant reduction in complex I activity after low-dose, chronic administr ation. Interestingly, an increase in the activity of cytochrome-c oxid ase (complex IV), probably reflecting enhanced functional neuronal act ivity, was observed in the frontal cortex of all chronically treated a nimals, an effect that is unlikely to result from compensation for the inhibition of complex I. Results suggest that previous findings, in w hich a reduction in the activity of cytochrome-c oxidase was observed in postmortem brain samples from schizophrenics, are not dependent on treatment with neuroleptics.