Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder
Tourette’s syndrome (TS) is a neurodevelopmental disorder characterized primarily by motor and vocal tics. Comorbidities such as attention deficit and hyperactivity disorder (ADHD) are observed in over 50% of TS patients. We applied aripiprazole in a juvenile rat model that displays motor tics and h...
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doaj-3bf8ffa9ef39466cbc7d018f669ac0372020-11-24T22:51:25ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-02-01910.3389/fneur.2018.00059332226Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity DisorderFrancesca Rizzo0Francesca Rizzo1Ester Nespoli2Alireza Abaei3Alireza Abaei4Izhar Bar-Gad5Dinesh K. Deelchand6Jörg Fegert7Volker Rasche8Volker Rasche9Bastian Hengerer10Tobias M. Boeckers11Department for Child and Adolescent Psychiatry and Psychotherapy, Ulm University, Ulm, GermanyInstitute of Anatomy and Cell Biology, Ulm University, Ulm, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, CNS Diseases, Biberach an der Riss, GermanyCore Facility Small Animal Imaging, Ulm University, Ulm, GermanyDepartment of Internal Medicine II, Ulm University Medical Center, Ulm, GermanyLeslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, IsraelCenter for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United StatesDepartment for Child and Adolescent Psychiatry and Psychotherapy, Ulm University, Ulm, GermanyCore Facility Small Animal Imaging, Ulm University, Ulm, GermanyDepartment of Internal Medicine II, Ulm University Medical Center, Ulm, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, CNS Diseases, Biberach an der Riss, GermanyInstitute of Anatomy and Cell Biology, Ulm University, Ulm, GermanyTourette’s syndrome (TS) is a neurodevelopmental disorder characterized primarily by motor and vocal tics. Comorbidities such as attention deficit and hyperactivity disorder (ADHD) are observed in over 50% of TS patients. We applied aripiprazole in a juvenile rat model that displays motor tics and hyperactivity. We additionally assessed the amount of ultrasonic vocalizations (USVs) as an indicator for the presence of vocal tics and evaluated the changes in the striatal neurometabolism using in vivo proton magnetic resonance spectroscopy (1H-MRS) at 11.7T. Thirty-one juvenile spontaneously hypertensive rats (SHRs) underwent bicuculline striatal microinjection and treatment with either aripiprazole or vehicle. Control groups were sham operated and sham injected. Behavior, USVs, and striatal neurochemical profile were analyzed at early, middle, and late adolescence (postnatal days 35 to 50). Bicuculline microinjections in the dorsolateral striatum induced motor tics in SHR juvenile rats. Acute aripiprazole administration selectively reduced both tic frequency and latency, whereas stereotypies, USVs, and hyperactivity remained unaltered. The striatal neurochemical profile was only moderately altered after tic-induction and was not affected by systemic drug treatment. When applied to a young rat model that provides high degrees of construct, face, and predictive validity for TS and comorbid ADHD, aripiprazole selectively reduces motor tics, revealing that tics and stereotypies are distinct phenomena in line with clinical treatment of patients. Finally, our 1H-MRS results suggest a critical revision of the striatal role in the hypothesized cortico-striatal dysregulation in TS pathophysiology.http://journal.frontiersin.org/article/10.3389/fneur.2018.00059/fulladolescencespontaneously hypertensive rat1H magnetic resonance spectroscopyattention-deficit/hyperactivity disorderTourette’s syndromestriatum |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francesca Rizzo Francesca Rizzo Ester Nespoli Alireza Abaei Alireza Abaei Izhar Bar-Gad Dinesh K. Deelchand Jörg Fegert Volker Rasche Volker Rasche Bastian Hengerer Tobias M. Boeckers |
spellingShingle |
Francesca Rizzo Francesca Rizzo Ester Nespoli Alireza Abaei Alireza Abaei Izhar Bar-Gad Dinesh K. Deelchand Jörg Fegert Volker Rasche Volker Rasche Bastian Hengerer Tobias M. Boeckers Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder Frontiers in Neurology adolescence spontaneously hypertensive rat 1H magnetic resonance spectroscopy attention-deficit/hyperactivity disorder Tourette’s syndrome striatum |
author_facet |
Francesca Rizzo Francesca Rizzo Ester Nespoli Alireza Abaei Alireza Abaei Izhar Bar-Gad Dinesh K. Deelchand Jörg Fegert Volker Rasche Volker Rasche Bastian Hengerer Tobias M. Boeckers |
author_sort |
Francesca Rizzo |
title |
Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder |
title_short |
Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder |
title_full |
Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder |
title_fullStr |
Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder |
title_full_unstemmed |
Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder |
title_sort |
aripiprazole selectively reduces motor tics in a young animal model for tourette’s syndrome and comorbid attention deficit and hyperactivity disorder |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2018-02-01 |
description |
Tourette’s syndrome (TS) is a neurodevelopmental disorder characterized primarily by motor and vocal tics. Comorbidities such as attention deficit and hyperactivity disorder (ADHD) are observed in over 50% of TS patients. We applied aripiprazole in a juvenile rat model that displays motor tics and hyperactivity. We additionally assessed the amount of ultrasonic vocalizations (USVs) as an indicator for the presence of vocal tics and evaluated the changes in the striatal neurometabolism using in vivo proton magnetic resonance spectroscopy (1H-MRS) at 11.7T. Thirty-one juvenile spontaneously hypertensive rats (SHRs) underwent bicuculline striatal microinjection and treatment with either aripiprazole or vehicle. Control groups were sham operated and sham injected. Behavior, USVs, and striatal neurochemical profile were analyzed at early, middle, and late adolescence (postnatal days 35 to 50). Bicuculline microinjections in the dorsolateral striatum induced motor tics in SHR juvenile rats. Acute aripiprazole administration selectively reduced both tic frequency and latency, whereas stereotypies, USVs, and hyperactivity remained unaltered. The striatal neurochemical profile was only moderately altered after tic-induction and was not affected by systemic drug treatment. When applied to a young rat model that provides high degrees of construct, face, and predictive validity for TS and comorbid ADHD, aripiprazole selectively reduces motor tics, revealing that tics and stereotypies are distinct phenomena in line with clinical treatment of patients. Finally, our 1H-MRS results suggest a critical revision of the striatal role in the hypothesized cortico-striatal dysregulation in TS pathophysiology. |
topic |
adolescence spontaneously hypertensive rat 1H magnetic resonance spectroscopy attention-deficit/hyperactivity disorder Tourette’s syndrome striatum |
url |
http://journal.frontiersin.org/article/10.3389/fneur.2018.00059/full |
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