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 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.
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Authors | J L Silverman, M C Pride, J E Hayes, K R Puhger, H M Butler-Struben, S Baker, J N Crawley |
Journal | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
(Neuropsychopharmacology)
Vol. 40
Issue 9
Pg. 2228-39
(Aug 2015)
ISSN: 1740-634X [Electronic] England |
PMID | 25754761
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- GABA-B Receptor Agonists
- Baclofen
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Topics |
- Analysis of Variance
- Animals
- Autistic Disorder
(complications, genetics)
- Baclofen
(therapeutic use)
- Cumulative Trauma Disorders
(drug therapy, 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, etiology)
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