Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice
Abstract
Reduced serotonin transporter (5-HTT) expression is associated with abnormal affective and anxiety-like symptoms in humans and rodents, but the mechanism of this effect is unknown. Transient inhibition of 5-HTT during early development with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced abnormal emotional behaviors in adult mice. This effect mimicked the behavioral phenotype of mice genetically deficient in 5-HTT expression. These findings indicate a critical role of serotonin in the maturation of brain systems that modulate emotional function in the adult and suggest a developmental mechanism to explain how low-expressing 5-HTT promoter alleles increase vulnerability to psychiatric disorders.
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Rodent studies suggested prenatal exposure to serotonergic drugs produced autism-like behaviors in offspring.
“Rodent studies nearly a decade ago suggested that prenatal exposure to serotonergic drugs yielded autism-like behaviors in offspring4.”
In both prior studies, risk was also observed with non-SSRIs, contrary to rodent model predictions.
“In both of these prior studies, contrary to predictions from rodent models 4, risk was also observed with non-SSRIs.”
Dayan and Huys [17] explained the serotonin-depression paradox by suggesting that people who experienced high levels of serotonin and exaggerated Pavlovian behavioural inhibition during early development would be most sensitive to effects of any interference with this inhibition in adulthood secondary to a drop in serotonin levels.
“Dayan and Huys [17] explained this paradox by suggesting that people who experienced high levels of serotonin and thus exaggerated Pavlovian behavioural inhibition during early development [32] would be most sensitive to the effects of any interference with this inhibition in adulthood secondary to a drop in serotonin levels [33], [34].”
From Bonsai trees in your head: how the pavlovian system sculpts goal-directed choices by pruning decision trees (2012) · cites this paper as [32]
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- Authors
- Ansorge, M. S., Zhou, M., Lira, A., Hen, R., & Gingrich, J. A.
- Affiliations
- Columbia University Irving Medical Center (US)
- Sackler Institute for Developmental Psychobiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
- Corresponding author
- Gingrich, Jay A.
- Venue
- Science
- Published
- 2004-10-29
- Volume
- 306
- Issue
- 5697
- Pages
- 879-881
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2011812102
- Cited by
- 817
- References
- 36
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 14 · 2023: 21 · 2022: 19 · 2021: 23 · 2020: 34 · 2019: 39 · 2018: 27 · 2017: 33 · 2016: 47 · 2015: 35 · 2014: 50 · 2013: 57 · 2012: 57
- FWCI
- 15.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- serotonin transporter, fluoxetine, emotional behavior, anxiety-like behavior, serotonin, brain development, psychiatric vulnerability
- MeSH terms
- Animals, Animals, Newborn, Anxiety, Avoidance Learning, Behavior, Animal, Brain, Central Nervous System, Emotions, Feeding Behavior, Fluoxetine, Humans, Membrane Glycoproteins, Motor Activity, Nerve Tissue Proteins, Polymorphism, Genetic, Random Allocation, Stress, Physiological, Selective Serotonin Reuptake Inhibitors, Membrane Transport Proteins, Membrane Transport Modulators, Serotonin Plasma Membrane Transport Proteins, Mice
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