Biochemical and molecular effects of chronic haloperidol administration on brain and muscle mitochondria of rats

Antonio Barrientos, Concepció Marín, Òscar Miró, Jordi Casademont, Montserrat Gómez, Virginia Nunes, Eduardo Tolosa, Alvaro Urbano-Márquez, Francesc Cardellach

Research output: Contribution to journalArticle

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Abstract

The objectives of the current study were to evaluate (1) the respiratory rates and enzyme activities of brain and muscle mitochondria from rats chronically treated with haloperidol, (2) the protective role of dopamine (DA) D-1 (SKF38393) and D-2 (quinpirole) receptor agonists, and (3) the effect of haloperidol on the mitochondrial DNA (mtDNA) and protein synthesis. Thirty male Sprague-Dawley rats were subdivided into the following five groups: controls, haloperidol, haloperidol plus SKF38393, haloperidol plus quinpirole, and haloperidol plus SKF38393 and quinpirole. We compared the respiratory rates and enzymatic activities of brain and muscle mitochondria from controls with other groups. We finally analyzed the mitochondrial protein synthesis and mtDNA alterations (deletions, point mutations, and depletion) in two rats from each group. In brain but not in muscle from haloperidol-treated rats, we found a decrease of oxygen consumption rates using glutamate plus malate (-68 ± 35%, P < 0.05) and succinate (-78 ± 20%, P < 0.05) as substrates as well as low complex I, II, and V activities (-35 ± 15%, P < 0.05; -54 ± 13%, P < 0.05; and -60 ± 33%, P < 0.01; respectively). The administration of SKF38393 alone or together with quinpirole prevented most of haloperidol-induced effects, whereas the protective effects of quinpirole alone were lower. Brain mitochondrial protein synthesis was decreased in haloperidol-treated rats and was not prevented by SKF38393, quinpirole, or both. We did not find mtDNA abnormalities in brain or muscle mitochondria from haloperidol-treated rats. Chronic administration of haloperidol in rats is associated with a nonspecific deleterious effect in the activity of electron transport chain of brain, and this effect is only partially prevented by DA D-1 agonists. These results suggest that other mechanisms different from DA receptors pathway can contribute to the expression of behavioral supersensitivity.

Original languageEnglish
Pages (from-to)475-481
Number of pages7
JournalJournal of Neuroscience Research
Volume53
Issue number4
DOIs
StatePublished - Aug 15 1998

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Muscle Mitochondrion
Haloperidol
Quinpirole
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Brain
Mitochondrial Proteins
Mitochondrial DNA
Respiratory Rate
Dopamine
Sequence Deletion
Dopamine Receptors
Succinic Acid
Electron Transport
Point Mutation
Oxygen Consumption
Sprague Dawley Rats
Glutamic Acid

Keywords

  • Dopamine receptors
  • Haloperidol
  • Mitochondria
  • mtDNA
  • Respiratory chain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Biochemical and molecular effects of chronic haloperidol administration on brain and muscle mitochondria of rats. / Barrientos, Antonio; Marín, Concepció; Miró, Òscar; Casademont, Jordi; Gómez, Montserrat; Nunes, Virginia; Tolosa, Eduardo; Urbano-Márquez, Alvaro; Cardellach, Francesc.

In: Journal of Neuroscience Research, Vol. 53, No. 4, 15.08.1998, p. 475-481.

Research output: Contribution to journalArticle

Barrientos, Antonio ; Marín, Concepció ; Miró, Òscar ; Casademont, Jordi ; Gómez, Montserrat ; Nunes, Virginia ; Tolosa, Eduardo ; Urbano-Márquez, Alvaro ; Cardellach, Francesc. / Biochemical and molecular effects of chronic haloperidol administration on brain and muscle mitochondria of rats. In: Journal of Neuroscience Research. 1998 ; Vol. 53, No. 4. pp. 475-481.
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