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

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          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.

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          Author and article information

          Journal
          7605818
          1921
          Brain Res Bull
          Brain Res. Bull.
          Brain research bulletin
          0361-9230
          1873-2747
          10 August 2017
          15 May 2013
          July 2013
          03 September 2017
          : 96
          : 62-70
          Affiliations
          [a ]Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA, United States
          [b ]Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States
          Author notes
          [* ]Corresponding author at: Department of Psychiatry and Behavioral Sciences, 825 FairFax Avenue, Suite 710, Norfolk, VA 23507, United States. Tel.: +1 757 446 5888; Fax: +1 757 446 5918., deutscsi@ 123456evms.edu (S.I. Deutsch)
          Article
          PMC5581963 PMC5581963 5581963 nihpa898862
          10.1016/j.brainresbull.2013.05.003
          5581963
          23685206
          53756f8c-06d5-419a-a07d-b6dfc81574f7
          History
          Categories
          Article

          BTBR mice,Stereotypies,Sociability,NMDA receptor, d-Cycloserine

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