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 language | English (US) |
|---|---|
| Pages (from-to) | 2228-2239 |
| Number of pages | 12 |
| Journal | Neuropsychopharmacology |
| Volume | 40 |
| Issue number | 9 |
| DOIs | |
| State | Published - Mar 10 2015 |
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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 journal › Article
}
TY - JOUR
T1 - GABA B Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism
AU - Silverman, Jill L
AU - Pride, M. C.
AU - Hayes, J. E.
AU - Puhger, K. R.
AU - Butler-Struben, H. M.
AU - Baker, S.
AU - Crawley, Jacqueline
PY - 2015/3/10
Y1 - 2015/3/10
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84937164423&partnerID=8YFLogxK
U2 - 10.1038/npp.2015.66
DO - 10.1038/npp.2015.66
M3 - Article
C2 - 25754761
AN - SCOPUS:84937164423
VL - 40
SP - 2228
EP - 2239
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 9
ER -