Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice.
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.
Ansorge
Mark S
MS
Sackler Institute for Developmental Psychobiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Zhou
Mingming
M
Lira
Alena
A
Hen
René
R
Gingrich
Jay A
JA
D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002490:Central Nervous System / Q000187:drug effects / Q000254:growth & development; D004644:Emotions / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000009:adverse effects / Q000633:toxicity*; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011110:Polymorphism, Genetic; D011897:Random Allocation; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000633:toxicity*; D013312:Stress, Physiological
D005473:Fluoxetine; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human; C493231:Slc6a4 protein, mouse