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Perinatal reduction of functional serotonin transporters results in developmental delay

Yvet Kroeze1, Bart Dirven2, Stefan Janssen2

  • 1Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 EZ Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 GA Nijmegen, The Netherlands.

Neuropharmacology
|May 22, 2016
PubMed

Insights

Early-life reduction in serotonin transporter (5-HTT) function causes developmental delays but most behavioral effects normalize later. Lifelong 5-HTT inactivation impacts adult object recognition and directed behaviors.

Area of Science:

  • Neuroscience
  • Developmental Psychology
  • Pharmacology

Background:

  • Reduced serotonin transporter (5-HTT) function in early life is linked to neuropsychiatric disorders.
  • The impact of altered 5-HTT function on behavior across developmental stages remains understudied.

Purpose of the Study:

  • To investigate the effects of perinatal and lifelong 5-HTT inactivation on behavior throughout development.
  • To compare the behavioral outcomes of pharmacological and genetic 5-HTT inactivation.

Main Methods:

  • Rats were exposed perinatally to fluoxetine or vehicle, and genetic 5-HTT knockout (5-HTT-/-) and wild-type (5-HTT+/+) rats were used.
  • A comprehensive battery of behavioral tests assessed motor, olfactory, grooming, sensorimotor gating, and object-related behaviors across postnatal weeks, adolescence, and adulthood.
  • Developmental milestones including eye opening, reflex development, and body weight were monitored.

Main Results:

  • Both perinatal fluoxetine exposure and genetic 5-HTT inactivation led to developmental delays.
  • Most early-life behavioral alterations normalized by adulthood, except for hypo-locomotion.
  • Adolescent and adult 5-HTT-/- rats exhibited altered object-directed behavior and impaired novel object recognition.

Conclusions:

  • Perinatal and lifelong 5-HTT inactivation induce developmental delays, with most effects resolving over time.
  • Lifelong 5-HTT inactivation is associated with persistent changes in object recognition and directed behaviors in adulthood.
  • These findings enhance understanding of 5-HTT's role in behavioral development and potential long-term consequences of its inactivation.

Keywords:
Developmental delaySelective serotonin reuptake inhibitorSerotoninSerotonin transporter

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