Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice

• Published in: Science (American Association for the Advancement of Science) 2004-10, Vol.306 (5697), p.879-881
• Main Authors: Ansorge, Mark S., Zhou, Mingming, Lira, Alena, Hen, René, Gingrich, Jay A.
• Format: Article
• Language: English
• Subjects: Adults; Affective Behavior; Animal behavior; Animals; Animals, Newborn; Anxiety; Anxiety - chemically induced; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Behavioral neuroscience; Behavioral psychophysiology; Biological and medical sciences; Brain; Brain - drug effects; Brain - growth & development; Central Nervous System - drug effects; Central Nervous System - growth & development; Depression (Mood disorder); Depression (Psychology); Depression, Mental; Emotional development; Emotional expression; Emotional maturity; Emotions; Emotions - drug effects; Environmental Influences; Exhibits; Feeding Behavior - drug effects; Fluoxetine - adverse effects; Fluoxetine - toxicity; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetics; Genotype & phenotype; House mouse; Human genetics; Humans; Individualized Instruction; Inhibition; 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; Mental Disorders; Mice; Mice as laboratory animals; Mood disorders; Motor Activity - drug effects; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurotransmission and behavior; Neurotransmitters; Pharmacology; Physiological aspects; Polymorphism, Genetic; Psychiatry; Psychological Patterns; Psychological stress; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Random Allocation; Rodents; Serotonin Plasma Membrane Transport Proteins; Serotonin receptors; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - toxicity; Stress, Physiological
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1101678

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.