Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Jérôme Aj Becker (1) , Daniel Clesse (2) , Coralie Spiegelhalter (2) , Yannick Schwab (2) , Julie Le Merrer (1) , Brigitte L. Kieffer (2)

1 PRC - Physiologie de la reproduction et des comportements [Nouzilly]
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

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 À / À) 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 À / À 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.

Mots clés: mGluR4 positive allosteric modulator; reward deficiency; mu opioid receptor gene knockout; synaptic morphology; gene expression; cross-fostering

Domaines: Neurobiologie; Psychologie et comportements

Jérôme Aj Becker, Daniel Clesse, Coralie Spiegelhalter, Yannick Schwab, Julie Le Merrer, et al.. Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity. Neuropsychopharmacology, 2014, 39 (9), pp.2049-2060. ⟨10.1038/npp.2014.59⟩. ⟨hal-02266436⟩