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 journalArticle

77 Citations (Scopus)

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

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GABA-B Receptor Agonists
Baclofen
Autistic Disorder
Stereotyped Behavior
GABA-B Receptors
Fragile X Syndrome
Grooming
Inbred Strains Mice
Calcium Carbonate
Interpersonal Relations
Communication
Pharmacology
Autism Spectrum Disorder

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

GABA B Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism. / Silverman, Jill L; Pride, M. C.; Hayes, J. E.; Puhger, K. R.; Butler-Struben, H. M.; Baker, S.; Crawley, Jacqueline.

In: Neuropsychopharmacology, Vol. 40, No. 9, 10.03.2015, p. 2228-2239.

Research output: Contribution to journalArticle

Silverman, Jill L ; Pride, M. C. ; Hayes, J. E. ; Puhger, K. R. ; Butler-Struben, H. M. ; Baker, S. ; Crawley, Jacqueline. / GABA B Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism. In: Neuropsychopharmacology. 2015 ; Vol. 40, No. 9. pp. 2228-2239.
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