Diminished social interaction incentive contributes to social deficits in mouse models of autism spectrum disorder

Genes Brain Behav. 2020 Jan;19(1):e12610. doi: 10.1111/gbb.12610. Epub 2019 Nov 6.


One of the core symptoms of autism spectrum disorder (ASD) is impaired social interaction. Currently, no pharmacotherapies exist for this symptom due to complex biological underpinnings and distinct genetic models which fail to represent the broad disease spectrum. One convincing hypothesis explaining social deficits in human ASD patients is amotivation, however it is unknown whether mouse models of ASD represent this condition. Here we used two highly trusted ASD mouse models (male Shank3-deficient [Shank3+/ΔC ] mice modeling the monogenic etiology of ASD, and inbred BTBR mice [both male and female] modeling the idiopathic and highly polygenic pathology for ASD) to evaluate the level of motivation to engage in a social interaction. In the behavioral paradigms utilized, a social stimulus was placed in the open arm of the elevated plus maze (EPM), or the light compartment of the light-dark box (LDB). To engage in a social interaction, mice were thus required to endure innately aversive conditions (open areas, height, and/or light). In the modified EPM paradigm, both Shank3+/ΔC and BTBR mice demonstrated decreased open-arm engagement with a social stimulus but not a novel object, suggesting reduced incentive to engage in a social interaction in these models. However, these deficits were not expressed under the less severe aversive pressures of the LDB. Collectively, we show that ASD mouse models exhibit diminished social interaction incentive, and provide a new investigation strategy facilitating the study of the neurobiological mechanisms underlying social reward and motivation deficits in neuropsychiatric disorders.

Keywords: BTBR; Shank3; autism spectrum disorder; behavior model; elevated plus maze; incentive; light-dark box; motivation; sociability; social deficits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics*
  • Female
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Reward
  • Social Interaction*


  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Shank3 protein, mouse