GABAB Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism

Neuropsychopharmacology. 2015 Aug;40(9):2228-39. doi: 10.1038/npp.2015.66. Epub 2015 Mar 10.


Autism spectrum disorder (ASD) is diagnosed by two core behavioral criteria, unusual reciprocal social interactions and communication, and stereotyped, repetitive behaviors with restricted interests. Excitatory/inhibitory imbalance is a prominent hypothesis for the etiology of autism. The selective GABAB receptor agonist R-baclofen previously reversed social deficits and reduced repetitive behaviors in a mouse model of Fragile X syndrome, and Arbaclofen improved some clinical symptoms in some Fragile X and ASD patients. To evaluate R-baclofen in a broader range of mouse models of ASD, we tested both the R-baclofen enantiomer and the less potent S-baclofen enantiomer in two inbred strains of mice that display low sociability and/or high repetitive or stereotyped behaviors. R-baclofen treatment reversed social approach deficits in BTBR T+ Itpr3tf/J (BTBR), reduced repetitive self-grooming and high marble burying scores in BTBR, and reduced stereotyped jumping in C58/J (C58), at nonsedating doses. S-baclofen produced minimal effects at the same doses. These findings encourage investigations of R-baclofen in other preclinical model systems. Additional clinical studies may be warranted to further evaluate the hypothesis that the GABAB receptor represents a promising pharmacological target for treating appropriately stratified subsets of individuals with ASD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Autistic Disorder / complications
  • Autistic Disorder / genetics
  • Baclofen / therapeutic use*
  • Cumulative Trauma Disorders / drug therapy*
  • Cumulative Trauma Disorders / etiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • GABA-B Receptor Agonists / therapeutic use*
  • Grooming / drug effects
  • Locomotion / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants
  • Social Behavior Disorders / drug therapy*
  • Social Behavior Disorders / etiology


  • GABA-B Receptor Agonists
  • Baclofen