title: GABAB Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism.
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.
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Silverman
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Pride
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Hayes
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Puhger
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Butler-Struben
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Baker
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Crawley
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001321:Autistic Disorder / Q000150:complications / Q000235:genetics; D001418:Baclofen / Q000627:therapeutic use*; D012090:Cumulative Trauma Disorders / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D058786:GABA-B Receptor Agonists / Q000627:therapeutic use*; D006120:Grooming / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D012920:Social Behavior Disorders / Q000188:drug therapy* / Q000209:etiology
chemical_list: D058786:GABA-B Receptor Agonists; D001418:Baclofen