Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity.

TitleAutistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity.
Publication TypeJournal Article
Year of Publication2014
AuthorsBecker JAJ, Clesse D, Spiegelhalter C, Schwab Y, Le Merrer J, Kieffer BL
JournalNeuropsychopharmacology
Volume39
Issue9
Pagination2049-60
Date Published2014 Aug
ISSN1740-634X
KeywordsAggression, Anilides, Animals, Anxiety, Behavior, Animal, Brain, Child Development Disorders, Pervasive, Convulsants, Cyclohexanecarboxylic Acids, Disease Models, Animal, Excitatory Amino Acid Agents, Female, Male, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Pentylenetetrazole, Receptors, Metabotropic Glutamate, Receptors, Opioid, mu, Seizures, Social Behavior
Abstract

The etiology of Autism Spectrum Disorders (ASDs) remains largely unknown. Identifying vulnerability genes for autism represents a major challenge in the field and allows the development of animal models for translational research. Mice lacking the mu opioid receptor gene (Oprm1(-/-)) were recently proposed as a monogenic mouse model of autism, based on severe deficits in social behavior and communication skills. We confirm this hypothesis by showing that adult Oprm1(-/-) animals recapitulate core and multiple comorbid behavioral symptoms of autism and also display anatomical, neurochemical, and genetic landmarks of the disease. Chronic facilitation of mGluR4 signaling, which we identified as a novel pharmacological target in ASDs in these mice, was more efficient in alleviating behavioral deficits than the reference molecule risperidone. Altogether, our data provide first evidence that disrupted mu opioid receptor signaling is sufficient to trigger a comprehensive autistic syndrome, maybe through blunted social reward processes, and this mouse model opens promising avenues for therapeutic innovation.

DOI10.1038/npp.2014.59
Alternate JournalNeuropsychopharmacology
PubMed ID24619243
PubMed Central IDPMC4104328
Grant ListP50 DA005010 / DA / NIDA NIH HHS / United States

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