OCD candidate gene SLC1A1 /EAAT3 impacts basal ganglia-mediated activity and stereotypic behavior

Proceedings of the National Academy of Sciences of the United States of America
Isaac D ZikeJeremy Veenstra-VanderWeele

Abstract

Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1). However, no previous studies have investigated EAAT3 in basal ganglia circuits or in relation to OCD-related behavior. Here, we report a model of Slc1a1 loss based on an excisable STOP cassette that yields successful ablation of EAAT3 expression and function. Using amphetamine as a probe, we found that EAAT3 loss prevents expected increases in (i) locomotor activity, (ii) stereotypy, and (iii) immediate early gene induction in the dorsal striatum following amphetamine administration. Further, Slc1a1-STOP mice showed diminished grooming in an SKF-38393 challenge experiment, a pharmacologic model of OCD-like grooming behavior. This reduced grooming is accompanied by reduced dopamine D1 receptor binding in the d...Continue Reading

References

Sep 19, 1997·Archives of General Psychiatry·D R RosenbergB Birmaher
Jul 13, 2002·American Journal of Medical Genetics·Gregory L HannaEdwin H Cook
Jul 24, 2004·American Journal of Human Genetics·Virginia L WillourGerald Nestadt
Sep 25, 2004·Journal of Clinical Psychology·Darin D DoughertyMichael A Jenike
Mar 2, 2006·Psychiatry Research·Stephen P WhitesideJonathan S Abramowitz
Jul 5, 2006·Archives of General Psychiatry·Paul Daniel ArnoldJames L Kennedy
Sep 27, 2007·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·S Evelyn StewartDavid L Pauls
Apr 17, 2008·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·David L Pauls
Apr 30, 2008·International Journal of Psychiatry in Medicine·Humberto C PárragaDavid K Harris
Jan 20, 2009·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Y Y ShugartG Nestadt
Nov 3, 2009·The British Journal of Psychiatry : the Journal of Mental Science·Joaquim Radua, David Mataix-Cols
Nov 20, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Annalisa ScimemiJeffrey S Diamond
Mar 30, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Jack SamuelsGerald Nestadt
Mar 30, 2011·Annals of Neurology·Ari E BermanRaymond A Swanson
Nov 19, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Yasue HoriuchiTadao Arinami
Jan 6, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Susanne E AhmariH Blair Simpson
Apr 28, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Silvia HolmsethNiels C Danbolt
May 24, 2012·Psychiatric Genetics·Jeremy Veenstra-VanderWeelePaul D Arnold
Jan 24, 2013·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Marina Myles-WorsleyFrank A Middleton
Apr 23, 2013·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·S E StewartC A Mathews
Jul 12, 2013·Scandinavian Journal of Psychology·Winand H Dittrich, Thomas Johansen

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Citations

Apr 13, 2019·Autism Research : Official Journal of the International Society for Autism Research·Allison M J AnackerMichael D Saxe
Dec 13, 2019·Pharmacological Reviews·Henry SzechtmanKurt Leroy Hoffman
Sep 14, 2018·F1000Research·Andreas HartmannKevin J Black
Jan 10, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Claudia Delgado-AcevedoPablo R Moya
Dec 6, 2019·Frontiers in Pharmacology·Angélica P EscobarPablo R Moya
May 1, 2021·Frontiers in Cellular Neuroscience·Renae M RyanAnnalisa Scimemi
Jul 9, 2021·Frontiers in Cellular Neuroscience·Angélica P EscobarPablo R Moya

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