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Kesić M, Mokrović G, Tvrdeić A, et al. Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model. Front Psychiatry. 2021;12:741222doi: 10.3389/fpsyt.2021.741222.
Kesić, M., Mokrović, G., Tvrdeić, A., Miše, B., Štefulj, J., & Čičin-Šain, L. (2021). Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model. Frontiers in psychiatry, 12741222. https://doi.org/10.3389/fpsyt.2021.741222
Kesić, Maja, et al. "Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model." Frontiers in psychiatry vol. 12 (2021): 741222. doi: https://doi.org/10.3389/fpsyt.2021.741222
Kesić M, Mokrović G, Tvrdeić A, Miše B, Štefulj J, Čičin-Šain L. Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model. Front Psychiatry. 2021 Oct 01;12:741222. doi: 10.3389/fpsyt.2021.741222. eCollection 2021. PMID: 34658974; PMCID: PMC8517234.
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Front Psychiatry. 2021 Oct 01;12:741222. doi: 10.3389/fpsyt.2021.741222. eCollection 2021.

Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model.

Frontiers in psychiatry

Maja Kesić, Gordana Mokrović, Ante Tvrdeić, Branko Miše, Jasminka Štefulj, Lipa Čičin-Šain

Affiliations

  1. Laboratory for Neurochemistry and Molecular Neurobiology, Department of Molecular Biology, Ru?er Boškovi? Institute, Zagreb, Croatia.
  2. Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
  3. University Hospital for Infectious Diseases, Zagreb, Croatia.

PMID: 34658974 PMCID: PMC8517234 DOI: 10.3389/fpsyt.2021.741222

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medications for the treatment of mood disorders. Yet, individual response to SSRIs is highly variable, with only a portion of patients showing the desired therapeutic effect. To better understand the molecular basis underlying individual variability in response to SSRIs, here we comparatively studied behavioral and molecular consequences of chronic treatment with fluoxetine, a widely used SSRI, in two sublines of rats with constitutionally different serotonin (5HT) homeostasis: the high-5HT and low-5HT sublines. Platelet 5HT levels, a recognized indicator of SSRI efficacy, were decreased by fluoxetine treatment in both 5HT-sublines. On the other hand, biologically active plasma 5HT levels were reduced only in high-5HT rats. The anxiolytic effect of fluoxetine was also evident only in high-5HT rats, as supported by spatio-temporal and ethological behavioral measures in the elevated plus maze (EPM) test and exploratory behavior measures in the open field (OF) test. None of the behavioral EPM or OF measures were significantly altered by fluoxetine treatment in low-5HT rats. Unexpectedly, 5HT levels in cerebral cortices tended to be reduced only in low-5HT rats. Moreover, the effects of fluoxetine on cortical expression levels of 5HT-related proteins were also present only in low-5HT rats, with serotonin transporter (

Copyright © 2021 Kesić, Mokrović, Tvrdeić, Miše, Štefulj and Čičin-Šain.

Keywords: 5-HT; SSRI; animal model; anxiety; depression; serotonin transporter

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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