Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice

Mark S Ansorge; Mingming Zhou; Alena Lira; René Hen; Jay A Gingrich

doi:10.1126/science.1101678

Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice

Science. 2004 Oct 29;306(5697):879-81. doi: 10.1126/science.1101678.

Authors

Mark S Ansorge¹, Mingming Zhou, Alena Lira, René Hen, Jay A Gingrich

Affiliation

¹ Sackler Institute for Developmental Psychobiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

PMID: 15514160
DOI: 10.1126/science.1101678

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.

MeSH terms

Animals
Animals, Newborn
Anxiety* / chemically induced
Avoidance Learning / drug effects
Behavior, Animal / drug effects
Brain / drug effects
Brain / growth & development
Central Nervous System / drug effects
Central Nervous System / growth & development
Emotions* / drug effects
Feeding Behavior / drug effects
Fluoxetine / adverse effects
Fluoxetine / toxicity*
Humans
Membrane Glycoproteins / antagonists & inhibitors
Membrane Glycoproteins / genetics
Membrane Glycoproteins / physiology*
Membrane Transport Modulators
Membrane Transport Proteins / antagonists & inhibitors
Membrane Transport Proteins / genetics
Membrane Transport Proteins / physiology*
Mice
Motor Activity / drug effects
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / physiology*
Polymorphism, Genetic
Random Allocation
Selective Serotonin Reuptake Inhibitors / adverse effects
Selective Serotonin Reuptake Inhibitors / toxicity*
Serotonin Plasma Membrane Transport Proteins
Stress, Physiological

Substances

Membrane Glycoproteins
Membrane Transport Modulators
Membrane Transport Proteins
Nerve Tissue Proteins
SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Slc6a4 protein, mouse
Fluoxetine