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Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice
Mark S. Ansorge,1,2,3
Mingming Zhou,2,3
Alena Lira,2,3
René Hen,2,4
Jay A. Gingrich2,3*
Abstract:
Reduced serotonin transporter (5-HTT) expression is associatedwith abnormal affective and anxiety-like symptoms in humansand rodents, but the mechanism of this effect is unknown. Transientinhibition of 5-HTT during early development with fluoxetine,a commonly used serotonin selective reuptake inhibitor, producedabnormal emotional behaviors in adult mice. This effect mimickedthe behavioral phenotype of mice genetically deficient in 5-HTTexpression. These findings indicate a critical role of serotoninin the maturation of brain systems that modulate emotional functionin the adult and suggest a developmental mechanism to explainhow low-expressing 5-HTT promoter alleles increase vulnerabilityto psychiatric disorders.
1 Sackler Institute for Developmental Psychobiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. 2 Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. 3 Department of Developmental Psychobiology, New York State Psychiatric Institute, New York, NY 10032, USA. 4 Department of Neurobiology and Behavior, New York State Psychiatric Institute, New York, NY 10032, USA.
* To whom correspondence should be addressed. E-mail: jag46{at}columbia.edu
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