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

Jill L Silverman, M. C. Pride, J. E. Hayes, K. R. Puhger, H. M. Butler-Struben, S. Baker, Jacqueline Crawley

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

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 GABA B 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 GABA B receptor represents a promising pharmacological target for treating appropriately stratified subsets of individuals with ASD.

Original languageEnglish (US)
Pages (from-to)2228-2239
Number of pages12
JournalNeuropsychopharmacology
Volume40
Issue number9
DOIs
StatePublished - Mar 10 2015

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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