D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling

Brain Res Bull. 2013 Jul;96:62-70. doi: 10.1016/j.brainresbull.2013.05.003. Epub 2013 May 15.

Abstract

The genetically inbred BTBR T+ Itpr3tf/J (BTBR) mouse is a proposed model of autism spectrum disorders (ASDs). Similar to several syndromic forms of ASDs, mTOR activity may be enhanced in this mouse strain as a result of increased Ras signaling. Recently, D-cycloserine, a partial glycineB site agonist that targets the NMDA receptor, was shown to improve the sociability of the Balb/c mouse strain, another proposed genetically inbred model of ASDs. NMDA receptor activation is an important regulator of mTOR signaling activity. Given the ability of D-cycloserine to improve the sociability of the Balb/c mouse strain and the regulatory role of the NMDA receptor in mTOR signaling, we wondered if D-cycloserine would improve the impaired sociability of the BTBR mouse strain. D-Cycloserine (320 mg/kg, ip) improved measures of sociability in a standard sociability paradigm and spontaneous grooming that emerged during social interaction with an ICR stimulus mouse in the BTBR strain; however, similar effects were observed in the Swiss Webster comparator strain, raising questions about their strain-selectivity. Importantly, the profile of D-cycloserine's effects on both measures of sociability and stereotypies is consistent with that of a desired medication for ASDs; specifically, a desired medication would not improve sociability at the expense of worsening stereotypic behaviors or vice versa.

Keywords: BTBR mice; NMDA receptor; Sociability; Stereotypies; d-Cycloserine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Child Development Disorders, Pervasive / drug therapy*
  • Cycloserine / pharmacology*
  • Disease Models, Animal
  • Grooming / physiology
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Social Behavior*
  • Stereotyped Behavior / drug effects*
  • TOR Serine-Threonine Kinases / drug effects
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Cycloserine
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse