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Modulation of serotonin transporter expression by escitalopram under inflammation.

Publication ,  Journal Article
Mena, S; Cruikshank, A; Best, J; Nijhout, HF; Reed, MC; Hashemi, P
Published in: Communications biology
June 2024

Selective serotonin reuptake inhibitors (SSRIs) are widely used for depression based on the monoamine deficiency hypothesis. However, the clinical use of these agents is controversial, in part because of their variable clinical efficacy and in part because of their delayed onset of action. Because of the complexities involved in replicating human disease and clinical dosing in animal models, the scientific community has not reached a consensus on the reasons for these phenomena. In this work, we create a theoretical hippocampal model incorporating escitalopram's pharmacokinetics, pharmacodynamics (competitive and non-competitive inhibition, and serotonin transporter (SERT) internalization), inflammation, and receptor dynamics. With this model, we simulate chronic oral escitalopram in mice showing that days to weeks are needed for serotonin levels to reach steady-state. We show escitalopram's chemical efficacy is diminished under inflammation. Our model thus offers mechanisms for how chronic escitalopram affects brain serotonin, emphasizing the importance of optimized dose and time for future antidepressant discoveries.

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Published In

Communications biology

DOI

EISSN

2399-3642

ISSN

2399-3642

Publication Date

June 2024

Volume

7

Issue

1

Start / End Page

710

Related Subject Headings

  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Selective Serotonin Reuptake Inhibitors
  • Mice
  • Inflammation
  • Humans
  • Hippocampus
  • Escitalopram
  • Citalopram
  • Animals
 

Citation

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Mena, S., Cruikshank, A., Best, J., Nijhout, H. F., Reed, M. C., & Hashemi, P. (2024). Modulation of serotonin transporter expression by escitalopram under inflammation. Communications Biology, 7(1), 710. https://doi.org/10.1038/s42003-024-06240-3
Mena, Sergio, Allison Cruikshank, Janet Best, H. F. Nijhout, Michael C. Reed, and Parastoo Hashemi. “Modulation of serotonin transporter expression by escitalopram under inflammation.Communications Biology 7, no. 1 (June 2024): 710. https://doi.org/10.1038/s42003-024-06240-3.
Mena S, Cruikshank A, Best J, Nijhout HF, Reed MC, Hashemi P. Modulation of serotonin transporter expression by escitalopram under inflammation. Communications biology. 2024 Jun;7(1):710.
Mena, Sergio, et al. “Modulation of serotonin transporter expression by escitalopram under inflammation.Communications Biology, vol. 7, no. 1, June 2024, p. 710. Epmc, doi:10.1038/s42003-024-06240-3.
Mena S, Cruikshank A, Best J, Nijhout HF, Reed MC, Hashemi P. Modulation of serotonin transporter expression by escitalopram under inflammation. Communications biology. 2024 Jun;7(1):710.

Published In

Communications biology

DOI

EISSN

2399-3642

ISSN

2399-3642

Publication Date

June 2024

Volume

7

Issue

1

Start / End Page

710

Related Subject Headings

  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Selective Serotonin Reuptake Inhibitors
  • Mice
  • Inflammation
  • Humans
  • Hippocampus
  • Escitalopram
  • Citalopram
  • Animals