title: D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Burket
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Benson
authors.forename: Amy H
authors.initials: AH
authors.lastname: Tang
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Deutsch
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy*; D003523:Cycloserine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006120:Grooming / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D003523:Cycloserine; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: BTBR mice; NMDA receptor; Sociability; Stereotypies; d-Cycloserine