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Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social

Camille N Pujol1,2, Lucie P Pellissier3,2, Céline Clément4

  • 1Médecine Translationelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Inserm U-964, CNRS UMR-7104, Université de Strasbourg, Illkirch, France.

Translational Psychiatry
|September 23, 2018
PubMed

Insights

Mice lacking the mu opioid receptor (MOR) showed autism-like behaviors. Positive reinforcement with food rewards improved their social interactions and normalized brain activity, suggesting reward pathways are key for social behavior in autism.

Area of Science:

  • Neuroscience
  • Behavioral Science
  • Genetics

Background:

  • The mu opioid receptor (MOR) is crucial for social behavior.
  • MOR dysfunction and altered reward processing are implicated in autism spectrum disorder (ASD).
  • Behavioral interventions for ASD utilize positive reinforcement, but their neurobiological basis is unclear.

Purpose of the Study:

  • To investigate the efficacy of applied behavior analysis (ABA)-based interventions in a mouse model of autism (Oprm1-/- mice).
  • To explore the role of reward processes in modulating social behavior deficits in ASD.
  • To elucidate the neurobiological mechanisms underlying ABA-based interventions.

Main Methods:

  • Back-translation of ABA-based interventions to Oprm1-/- mice.
  • Utilizing palatable food as a positive reinforcement for social interaction.
  • Assessing behavioral changes in social interaction and preference.
  • Analyzing gene expression related to neuronal activity, plasticity, and the oxytocin/vasopressin system in reward/social circuitry.

Main Results:

  • Oprm1-/- mice exhibited deficits in social interaction and preference, modeling ASD symptoms.
  • Associating food rewards with social encounters durably rescued social interaction and preference in Oprm1-/- mice.
  • Behavioral improvements were accompanied by normalization of neuronal activity/plasticity markers and oxytocin/vasopressin system genes in relevant brain regions.

Conclusions:

  • Reward processes are critical for driving social behavior, and their modulation can ameliorate social deficits in an autism model.
  • ABA-based interventions, leveraging positive reinforcement, show promise for treating social impairments in ASD.
  • This study highlights the potential of targeting reward pathways for novel therapeutic strategies in ASD.

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