title: Reversal of social deficits by subchronic oxytocin in two autism mouse models.
abstract: Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-d-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia-like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders.
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Eshelman School of Pharmacy, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Teng
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Viktoriya D
authors.initials: VD
authors.lastname: Nikolova
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Natallia V
authors.initials: NV
authors.lastname: Riddick
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Agster
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Crowley
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Lorinda K
authors.initials: LK
authors.lastname: Baker
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Koller
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Cort A
authors.initials: CA
authors.lastname: Pedersen
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Eshelman School of Pharmacy, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jarstfer
authors.affiliation: Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: ssmoy@med.unc.edu.
authors.forename: Sheryl S
authors.initials: SS
authors.lastname: Moy
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000503:physiopathology* / Q000517:prevention & control / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D010121:Oxytocin / Q000008:administration & dosage*; D065808:Prepulse Inhibition / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012919:Social Behavior
chemical_list: C121673:Gprin1 protein, mouse; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D010121:Oxytocin
keywords: Autism spectrum disorders; Clozapine; Oxytocin; Risperidone; Schizophrenia; Sociability