Behavior Genetics

, Volume 35, Issue 5, pp 615–629 | Cite as

Distinct Influences of Neonatal Epidermal Growth Factor Challenge on Adult Neurobehavioral Traits in Four Mouse Strains

  • Manavu Tohmi
  • Noriko Tsuda
  • Makoto Mizuno
  • Nobuyuki Takei
  • Paul W. Frankland
  • Hiroyuki Nawa

Epidermal growth factor (EGF) receptor (ErbB1) signals regulate dopaminergic development and function and are implicated in schizophrenia. We evaluated genetic effects on neurobehavioral changes induced by neonatal EGF administration, using four mouse strains. Subcutaneous EGF administration increased phosphorylation of brain ErbB1 in all strains, although DBA/2 and C57BL/6 mice had lower basal phosphorylation. Neonatal EGF treatment differentially influenced physical and behavioral/cognitive development, depending on mouse strain. Prepulse inhibition was decreased in DBA/2 and C57BL/6 mice but not C3H/He and ddY mice. Locomotor activity was accelerated in DBA/2 mice, but reduced in ddY mice. EGF treatment enhanced fear-learning performance with a tone cue in DBA/2 mice, but decreased performance with tone and context cues in C3H/He and ddY mice, respectively. The strain-dependent behavioral sensitivity was correlated with basal ErbB1 phosphorylation. Genetic components regulating brain ErbB1 signaling strongly influence the direction and strength of behavioral responses stemming from the neonatal neurotrophic perturbation.


Animal behavior cytokine environment genetic influence neurotrophic factor body weight schizophrenia 


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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Manavu Tohmi
    • 1
  • Noriko Tsuda
    • 1
  • Makoto Mizuno
    • 1
  • Nobuyuki Takei
    • 1
  • Paul W. Frankland
    • 2
  • Hiroyuki Nawa
    • 1
  1. 1.Division of Molecular Neurobiology, Brain Research InstituteNiigata UniversityNiigataJapan
  2. 2.Department of Neurobiology, Psychiatry, and Psychology, Brain Research InstituteUniversity of CaliforniaLos AngelesUSA

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