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

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Jill L SilvermanJacqueline N Crawley

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 GAB...Continue Reading

References

Jan 1, 1983·British Journal of Pharmacology·N G BoweryA L Hudson
Jan 1, 1993·Annual Review of Pharmacology and Toxicology·N G Bowery
Apr 17, 1998·American Journal of Medical Genetics·R J SchroerR E Stevenson
Nov 11, 2003·Genes, Brain, and Behavior·J L R Rubenstein, M M Merzenich
Sep 4, 2004·Genes, Brain, and Behavior·J J NadlerJ N Crawley
Sep 25, 2004·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Jacob L McCauleyJames S Sutcliffe
Aug 5, 2005·American Journal of Human Genetics·D Q MaM A Pericak-Vance
Mar 25, 2006·Journal of Medical Genetics·J B VincentS W Scherer
Sep 15, 2006·Behavioural Brain Research·Sheryl S MoyJacqueline N Crawley
Nov 14, 2006·Behavioural Brain Research·Valerie J BolivarJennifer L Phoenix
Feb 6, 2007·Current Opinion in Neurobiology·Daniel H Geschwind, Pat Levitt
Jun 15, 2007·Genes, Brain, and Behavior·H G McFarlaneJ N Crawley
Nov 6, 2007·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mu YangJacqueline N Crawley
Mar 26, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Soo-Jeong KimEdwin H Cook
Aug 30, 2008·PloS One·Maria Luisa ScattoniJacqueline N Crawley
Apr 10, 2009·Autism Research : Official Journal of the International Society for Autism Research·Jane YipGene J Blatt
Apr 11, 2009·Autism Research : Official Journal of the International Society for Autism Research·Kathryn K ChadmanJacqueline N Crawley
Jun 24, 2009·Current Opinion in Neurobiology·Thomas Bourgeron
Dec 25, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jill L SilvermanJacqueline N Crawley
Jun 19, 2010·Nature Reviews. Neuroscience·Jill L SilvermanJacqueline N Crawley
Jul 6, 2010·Behavioural Brain Research·Roger L H PobbeRobert J Blanchard
Jul 28, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jose Luis Olmos-SerranoMolly M Huntsman
Jul 29, 2010·Journal of Neurodevelopmental Disorders·Nadine GogollaTakao K Hensch
Sep 8, 2010·Behavioural Brain Research·Roger L H PobbeRobert J Blanchard
Sep 23, 2010·Molecular Autism·Randi HagermanPaul Hagerman
Sep 25, 2010·Pharmacology, Biochemistry, and Behavior·Kathryn K Chadman
Sep 28, 2010·Brain Research·Jill L SilvermanJacqueline N Crawley
Nov 3, 2010·Genes, Brain, and Behavior·B L PearsonR J Blanchard
Jul 29, 2011·Journal of Neurophysiology·Scott M PaluszkiewiczMolly M Huntsman
Aug 10, 2011·Neural Plasticity·Jocelyn J LeBlanc, Michela Fagiolini
Sep 9, 2011·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Gene J Blatt, S Hossein Fatemi
Sep 10, 2011·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Andrew H FairlessEdward S Brodkin

❮ Previous
Next ❯

Citations

Jan 28, 2016·Neuroscience and Biobehavioral Reviews·Chelcie F Heaney, Jefferson W Kinney
Jan 2, 2016·Progress in Neurobiology·Sarah Wurts BlackThomas S Kilduff
Jan 23, 2016·Behavioral and Brain Functions : BBF·Hyopil KimBong-Kiun Kaang
Sep 26, 2015·Genes, Brain, and Behavior·T M KazdobaJ N Crawley
Oct 4, 2016·Current Behavioral Neuroscience Reports·Amanda Crider, Anilkumar Pillai
Oct 4, 2016·Autism Research : Official Journal of the International Society for Autism Research·Russell G PortTimothy P L Roberts
Oct 18, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jeremy Veenstra-VanderWeeleRandall L Carpenter
Aug 31, 2016·Annual Review of Pharmacology and Toxicology·P H HutsonA J Cross
Feb 16, 2017·Annual Review of Animal Biosciences·Stacey J Sukoff Rizzo, Jacqueline N Crawley
Apr 30, 2017·The European Journal of Neuroscience·Yuri BozziSimona Casarosa
Mar 31, 2017·Naunyn-Schmiedeberg's Archives of Pharmacology·Olakunle James OnaolapoAdejoke Yetunde Onaolapo
Dec 9, 2017·Nature Reviews. Drug Discovery·Elizabeth M Berry-KravisSébastien Jacquemont
Oct 4, 2017·Expert Opinion on Drug Discovery·Kathryn K Chadman
Apr 26, 2016·Nature Neuroscience·Boaz Barak, Guoping Feng
May 23, 2018·Brain and Behavior·Shimriet ZeidlerRob Willemsen
Aug 24, 2018·Human Molecular Genetics·Annie Vogel CierniaJanine M LaSalle
Jan 18, 2019·Autism Research : Official Journal of the International Society for Autism Research·Maya A RhineJacqueline N Crawley
May 28, 2019·Expert Opinion on Drug Discovery·Kathryn K ChadmanRobert Feingold
Feb 13, 2019·The Journal of Pharmacology and Experimental Therapeutics·Mark H LewisAmber M Muehlmann
Jun 18, 2019·Chemical Biology & Drug Design·Zuleyma Martínez-CamposRodrigo Said Razo-Hernández
Nov 5, 2019·Current Pharmaceutical Design·Michael Telias
May 18, 2020·Fundamental & Clinical Pharmacology·Ismail O IsholaOlufunmilayo O Adeyemi
May 8, 2020·Journal of Neurochemistry·Katherine BonnycastleMichael A Cousin
Sep 2, 2020·Autism Research : Official Journal of the International Society for Autism Research·Justin K SiemannMark T Wallace
Sep 1, 2017·Annals of Neurology·Yongjin YooMurim Choi
May 28, 2019·The British Journal of Radiology·Russell G PortTimothy Pl Roberts
Mar 24, 2017·Human Molecular Genetics·Annie Vogel CierniaJanine M LaSalle

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autism: Treatment Targets

The absence of effective treatments for autism are due to the high clinical and genetic heterogeneity between affected individuals, restricted knowledge of the underlying pathophysiological mechanisms, and the lack of reliable diagnostic biomarkers. Identification of more homogenous biological subgroups is therefore essential for the development of novel treatments based on the molecular mechanisms underpinning autism and autism spectrum disorders. Find the latest research on autism treatment targets here.

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.

Related Papers

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Jill L SilvermanJacqueline N Crawley
Frontiers in Synaptic Neuroscience
Dionisio A AmodeoMichael E Ragozzino
© 2022 Meta ULC. All rights reserved