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c-Fos expression identifies brain areas activated in response to nortriptyline

Molecular Psychiatry volume 12, pages 613–615 (2007)Cite this article

This study shows that the administration of nortriptyline induces a pattern of c-Fos expression in the central nervous system of rats that resembles the typical, inverted U-shaped dose–response curve observed in clinical pharmacokinetic studies in humans. This did not occur following the use of desipramine, an alternative noradrenergic antidepressant drug whose clinical efficacy is not associated with this type of dose–response relationship.

Previous studies have suggested that there is an optimum range of nortriptyline blood levels, a therapeutic window above or below which depressed patients respond poorly or do not respond to treatment.1, 2 Our group has demonstrated that there is a biphasic curvilinear relationship between plasma levels of nortriptyline and behavior, using the tail suspension test,3 an animal model employed to screen for drugs with antidepressant effects. Although noradrenergic drugs are known to induce c-Fos expression in central neurons, only one study has investigated the effects of nortriptyline on the expression of brain c-Fos.4, 5 The magnitude of the therapeutic response observed with various doses of antidepressants may reflect differential activation of distinct brain areas for each dose used; therefore, we hypothesized that different doses of nortriptyline might induce different patterns of brain c-Fos expression in rats.

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Authors and Affiliations

  1. Department of Neuropsychiatry, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil

    M G Ribeiro, I R de Oliveira, D T Costa & L C Quarantini

  2. Department of Physiology, Health Sciences Institute, Federal University of Bahia, Salvador, Bahia, Brazil

    R C Santana, E de Castro e Silva & J B Fregoneze

Authors
  1. M G Ribeiro
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  2. I R de Oliveira
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  3. R C Santana
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  4. D T Costa
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  5. L C Quarantini
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  6. E de Castro e Silva
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  7. J B Fregoneze
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Correspondence to I R de Oliveira.

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Ribeiro, M., de Oliveira, I., Santana, R. et al. c-Fos expression identifies brain areas activated in response to nortriptyline. Mol Psychiatry 12, 613–615 (2007). https://doi.org/10.1038/sj.mp.4001989

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