Effect of antipsychotics on succinate dehydrogenase and cytochrome oxidase activities in rat brain

Abstract

Typical and atypical antipsychotic drugs have been shown to have different clinical, biochemical, and behavioral profiles. It is well described that impairment of metabolism, especially in the mitochondria, leads to oxidative stress and neuronal death and has been implicated in the pathogenesis of a number of diseases in the brain. Considering that some effects of chronic use of antipsychotic drugs are still not well known and that succinate dehydrogenase (SDH) and cytochrome oxidase (COX) are crucial enzymes of mitochondria, in this work, we evaluated the activities of these enzymes in rat brain after haloperidol, clozapine, olanzapine, or aripiprazole chronic administration. Adult male Wistar rats received daily injections of haloperidol (1.5 mg/kg), clozapine (25 mg/kg), olanzapine (2.5, 5, or 10 mg/kg), or aripiprazole (2, 10 or 20 mg/kg) for 28 days. We verified that COX was not altered by any drug tested. Moreover, our results demonstrated that the atypical antipsychotic olanzapine inhibited SDH in the cerebellum and aripiprazole increased the enzyme in the prefrontal cortex. We also observed that haloperidol inhibited SDH in the striatum and hippocampus, whereas clozapine inhibited the enzyme only in the striatum. These results showed that antipsychotic drugs altered SDH activity but not COX. In this context, haloperidol, olanzapine, and clozapine may impair energy metabolism in some brain areas.

Regulatory role of zinc during aluminium‐induced altered carbohydrate metabolism in rat brain

“…Furthermore, because of the increased activity of LDH, a large amount of pyruvate is converted into lactate instead of entering the TCA cycle, and as a result there is a decreased formation of substrate succinate for the enzyme activity. Similar findings with reduced SDH activity were shown by Streck et al (2007) and Sekhar et al (2010) during cypermethrin, sodium fluoride, and antipsychotics treatments. Altered activities of LDH and SDH suggest inhibition of energetic/glucose status with cytotoxicity in brain.…”

The effect of chronic tianeptine administration on the brain mitochondria: direct links with an animal model of depression

“…In addition, SDH activity is one of the most reliable markers of the efficiency of mitochondrial ATP production, and altered activity of this enzyme leads to impaired brain energy metabolism [37]. Most data indicated that chronic stress in rats decreased the activity of SDH in the brain [38].…”

The Phenomics and Expression Quantitative Trait Locus Mapping of Brain Transcriptomes Regulating Adaptive Divergence in Lake Whitefish Species Pairs (Coregonus sp.)

“…Cytochrome c oxidase was among the transcripts with eQTL in the genomic region containing locus CATA073.7 on LG 6m. This gene is a crucial mitochondrial enzyme that functions in the final step of the respiratory chain by carrying electrons from cytochrome c to molecular oxygen (Boekema and Braun 2007) and could be particularly important in high-energy-demanding brain tissue (Streck et al 2007). Cytochrome c oxidase emerges as an important metabolic candidate gene due to this colocalization, especially since CATA073.7 was an outlier in three separate species pairs, providing strong evidence that selection is responsible for elevated divergence at this region of the genome .…”