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Serotonin is a common thread linking different classes of antidepressants.

Publication ,  Journal Article
Witt, CE; Mena, S; Holmes, J; Hersey, M; Buchanan, AM; Parke, B; Saylor, R; Honan, LE; Berger, SN; Lumbreras, S; Nijhout, FH; Reed, MC ...
Published in: Cell chemical biology
December 2023

Depression pathology remains elusive. The monoamine hypothesis has placed much focus on serotonin, but due to the variable clinical efficacy of monoamine reuptake inhibitors, the community is looking for alternative therapies such as ketamine (neurogenesis theory of antidepressant action). There is evidence that different classes of antidepressants may affect serotonin levels; a notion we test here. We measure hippocampal serotonin in mice with voltammetry and study the effects of acute challenges of escitalopram, fluoxetine, reboxetine, and ketamine. We find that pseudo-equivalent doses of these drugs similarly raise ambient serotonin levels, despite their differing pharmacodynamics because of differences in Uptake 1 and 2, rapid SERT trafficking, and modulation of serotonin by histamine. These antidepressants have different pharmacodynamics but have strikingly similar effects on extracellular serotonin. Our findings suggest that serotonin is a common thread that links clinically effective antidepressants, synergizing different theories of depression (synaptic plasticity, neurogenesis, and the monoamine hypothesis).

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Published In

Cell chemical biology

DOI

EISSN

2451-9448

ISSN

2451-9456

Publication Date

December 2023

Volume

30

Issue

12

Start / End Page

1557 / 1570.e6

Related Subject Headings

  • Serotonin
  • Selective Serotonin Reuptake Inhibitors
  • Mice
  • Ketamine
  • Fluoxetine
  • Antidepressive Agents
  • Animals
  • 3404 Medicinal and biomolecular chemistry
  • 3101 Biochemistry and cell biology
 

Citation

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Witt, C. E., Mena, S., Holmes, J., Hersey, M., Buchanan, A. M., Parke, B., … Hashemi, P. (2023). Serotonin is a common thread linking different classes of antidepressants. Cell Chemical Biology, 30(12), 1557-1570.e6. https://doi.org/10.1016/j.chembiol.2023.10.009
Witt, Colby E., Sergio Mena, Jordan Holmes, Melinda Hersey, Anna Marie Buchanan, Brenna Parke, Rachel Saylor, et al. “Serotonin is a common thread linking different classes of antidepressants.Cell Chemical Biology 30, no. 12 (December 2023): 1557-1570.e6. https://doi.org/10.1016/j.chembiol.2023.10.009.
Witt CE, Mena S, Holmes J, Hersey M, Buchanan AM, Parke B, et al. Serotonin is a common thread linking different classes of antidepressants. Cell chemical biology. 2023 Dec;30(12):1557-1570.e6.
Witt, Colby E., et al. “Serotonin is a common thread linking different classes of antidepressants.Cell Chemical Biology, vol. 30, no. 12, Dec. 2023, pp. 1557-1570.e6. Epmc, doi:10.1016/j.chembiol.2023.10.009.
Witt CE, Mena S, Holmes J, Hersey M, Buchanan AM, Parke B, Saylor R, Honan LE, Berger SN, Lumbreras S, Nijhout FH, Reed MC, Best J, Fadel J, Schloss P, Lau T, Hashemi P. Serotonin is a common thread linking different classes of antidepressants. Cell chemical biology. 2023 Dec;30(12):1557-1570.e6.

Published In

Cell chemical biology

DOI

EISSN

2451-9448

ISSN

2451-9456

Publication Date

December 2023

Volume

30

Issue

12

Start / End Page

1557 / 1570.e6

Related Subject Headings

  • Serotonin
  • Selective Serotonin Reuptake Inhibitors
  • Mice
  • Ketamine
  • Fluoxetine
  • Antidepressive Agents
  • Animals
  • 3404 Medicinal and biomolecular chemistry
  • 3101 Biochemistry and cell biology