Serotonin is a common thread linking different classes of antidepressants
File(s)
Author(s)
Type
Journal Article
Abstract
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).
Date Issued
2023-12-21
Date Acceptance
2023-10-12
Citation
Cell Chemical Biology, 2023, 30 (12), pp.1557-1570
ISSN
2451-9448
Publisher
Cell Press
Start Page
1557
End Page
1570
Journal / Book Title
Cell Chemical Biology
Volume
30
Issue
12
Copyright Statement
© 2023 Elsevier Ltd.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37992715
PII: S2451-9456(23)00370-7
Subjects
ANIMAL-MODELS
Biochemistry & Molecular Biology
CELL-SURFACE EXPRESSION
ESCITALOPRAM
FORCED SWIMMING TEST
IN-VIVO
KETAMINE
Life Sciences & Biomedicine
NOREPINEPHRINE
RAT-BRAIN
REUPTAKE INHIBITORS
Science & Technology
TRANSPORTER
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2023-11-21