mGluR5-Antagonist Mediated Reversal of Elevated Stereotyped, Repetitive Behaviors in the VPA Model of Autism 英文参考文献.docVIP

mGluR5-AntagonistMediatedReversalofElevated Stereotyped,RepetitiveBehaviorsintheVPAModelof Autism MiliV.Mehta.,MichaelJ.Gandal.,StevenJ.Siegel* TranslationalNeuroscienceProgram,DepartmentofPsychiatry,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Autism spectrum disorders (ASD) are highly disabling developmental disorders with a population prevalence of 1–3%. Despiteastronggeneticetiology,therearenocurrenttherapeuticoptionsthattargetthecoresymptomsofASD.Emerging evidence suggests that dysfunction of glutamatergic signaling, in particular through metabotropic glutamate receptor 5 (mGluR5)receptors,maycontributetophenotypicdeficitsandmaybeappropriatetargetsforpharmacologicintervention. Thisstudyassessedthetherapeuticpotentialof2-methyl-6-phenylethyl-pyrididine(MPEP),anmGluR5-receptorantagonist, onrepetitiveandanxiety-likebehaviorsinthevalproicacid(VPA)mousemodelofautism.Micewereexposedprenatallyon dayE13toVPAandassessedforrepetitiveself-groomingandmarbleburyingbehaviorsasadults.Anxiety-likebehaviorand locomotor activity were measured in an open-field. VPA-exposed mice displayed increased repetitive and anxiety-like behaviors, consistent with previously published results. Across both marble burying and self-grooming assays, MPEP significantlyreducedrepetitivebehaviorsinVPA-treatedmice,buthadnoeffectonlocomotoractivity.Theseresultsare consistentwithemergingpreclinicalliteraturethatmGluR5-antagonistsmayhavetherapeuticefficacyforcoresymptomsof autism. Citation: Mehta MV, Gandal MJ, Siegel SJ (2011) mGluR5-Antagonist Mediated Reversal of Elevated Stereotyped, Repetitive Behaviors in the VPA Model of Autism.PLoSONE6(10):e26077.doi:10.1371/journal.pone.0026077 Editor:MelissaColeman,ClaremontColleges,UnitedStatesofAmerica ReceivedJune3,2011;AcceptedSeptember19,2011;PublishedOctober7,2011 Copyright: ? 2011 Mehta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unres