Reversal of social deficits by subchronic oxytocin in two autism mouse models
| Autor: | Kara L. Agster, Michael B. Jarstfer, James J. Crowley, Beverly H. Koller, Natallia V. Riddick, Lorinda K. Baker, Cort A. Pedersen, Viktoriya D. Nikolova, Brian L. Teng, Sheryl S. Moy |
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| Jazyk: | angličtina |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Autism Spectrum Disorder Nerve Tissue Proteins Hyperkinesis Oxytocin Choice Behavior Receptors N-Methyl-D-Aspartate Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine Stereotypy Genetic model medicine Animals Social Behavior Clozapine Prepulse inhibition Pharmacology Risperidone Behavior Animal Prepulse Inhibition Sociability Autism spectrum disorders medicine.disease Disease Models Animal 030104 developmental biology Endocrinology Schizophrenia Gene Knockdown Techniques Autism Female medicine.symptom Psychology 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists medicine.drug Clinical psychology |
| Zdroj: | Neuropharmacology. :61-71 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2015.12.025 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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