title: Developmental alterations in anxiety and cognitive behavior in serotonin transporter mutant mice.
abstract: BACKGROUND
  A promoter variant of the serotonin transporter (SERT) gene is known to affect emotional and cognitive regulation. In particular, the "short" allelic variant is implicated in the etiology of multiple neuropsychiatric disorders. Heterozygous (SERT(+/-)) and homozygous (SERT(-/-)) SERT mutant mice are valuable tools for understanding the mechanisms of altered SERT levels. Although these genetic effects are well investigated in adulthood, the developmental trajectory of altered SERT levels for behavior has not been investigated.
  
  
  OBJECTIVE
  We assessed anxiety-like and cognitive behaviors in SERT mutant mice in early adolescence and adulthood to examine the developmental consequences of reduced SERT levels. Spine density of pyramidal neurons was also measured in corticolimbic brain regions.
  
  
  RESULTS
  Adult SERT(-/-) mice exhibited increased anxiety-like behavior, but these differences were not observed in early adolescent SERT(-/-) mice. Conversely, SERT(+/-) and SERT(-/-) mice did display higher spontaneous alternation during early adolescence and adulthood. SERT(+/-) and SERT(-/-) also exhibited greater neuronal spine densities in the orbitofrontal but not the medial prefrontal cortices. Adult SERT(-/-) mice also showed an increased spine density in the basolateral amygdala.
  
  
  CONCLUSIONS
  Developmental alterations of the serotonergic system caused by genetic inactivation of SERT can have different influences on anxiety-like and cognitive behaviors through early adolescence into adulthood, which may be associated with changes of spine density in the prefrontal cortex and amygdala. The altered maturation of serotonergic systems may lead to specific age-related vulnerabilities to psychopathologies that develop during adolescence.
authors.affiliation: Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kasahara
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Murphy
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D049229:Dendritic Spines / Q000378:metabolism; D004644:Emotions / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017966:Pyramidal Cells / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins
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