title: Perinatal reduction of functional serotonin transporters results in developmental delay.
abstract: While there is strong evidence from rodent and human studies that a reduction in serotonin transporter (5-HTT) function in early-life can increase the risk for several neuropsychiatric disorders in adulthood, the effects of reduced 5-HTT function on behavior across developmental stages are underinvestigated. To elucidate how perinatal pharmacological and lifelong genetic inactivation of the 5-HTT affects behavior across development, we conducted a battery of behavioral tests in rats perinatally exposed to fluoxetine or vehicle and in 5-HTT(-/-) versus 5-HTT(+/+) rats. We measured motor-related behavior, olfactory function, grooming behavior, sensorimotor gating, object directed behavior and novel object recognition in the first three postnatal weeks and if possible the tests were repeated in adolescence and adulthood. We also measured developmental milestones such as eye opening, reflex development and body weight. We observed that both pharmacological and genetic inactivation of 5-HTT resulted in a developmental delay. Except for hypo-locomotion, most of the observed early-life effects were normalized later in life. In adolescence and adulthood we observed object directed behavior and decreased novel object recognition in the 5-HTT(-/-) rats, which might be related to the lifelong inactivation of 5-HTT. Together, these data provide an important contribution to the understanding of the effects of perinatal and lifelong 5-HTT inactivation on behavior across developmental stages.
authors.affiliation: Donders 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. Electronic address: Yvet.Kroeze@radboudumc.nl.
authors.forename: Yvet
authors.initials: Y
authors.lastname: Kroeze
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Dirven
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssen
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Kröhnke
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Barte
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Anthonieke
authors.initials: A
authors.lastname: Middelman
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 GA Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 GA Nijmegen, The Netherlands; Department of Molecular Developmental Biology, Faculty of Science, Radboud University Nijmegen, Radboud Institute for Molecular Life Sciences, 6525 GA Nijmegen, The Netherlands.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
mesh_terms: D000818:Animals; D002658:Developmental Disabilities / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Developmental delay; Selective serotonin reuptake inhibitor; Serotonin; Serotonin transporter