Aripiprazole selectively reduces motor tics in a young animal model for Tourette's syndrome and comorbid attention deficit and hyperactivity disorder

Francesca Rizzo, Ester Nespoli, Alireza Abaei, Izhar Bar-Gad, Dinesh K. Deelchand, Jörg Fegert, Volker Rasche, Bastian Hengerer, Tobias M. Boeckers

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number59
JournalFrontiers in Neurology
Volume9
Issue numberFEB
DOIs
StatePublished - Feb 13 2018

Fingerprint

Tics
Tourette Syndrome
Attention Deficit Disorder with Hyperactivity
Corpus Striatum
Animal Models
Ultrasonics
Bicuculline
Microinjections
Inbred SHR Rats
Hyperkinesis
Aripiprazole
Reproducibility of Results
Comorbidity
Therapeutics
Control Groups

Keywords

  • 1H magnetic resonance spectroscopy
  • Adolescence
  • Attention-deficit/hyperactivity disorder
  • Metabolite absolute concentration
  • Spontaneously hypertensive rat
  • Stereotypies
  • Striatum
  • Tourette's syndrome

Cite this

Aripiprazole selectively reduces motor tics in a young animal model for Tourette's syndrome and comorbid attention deficit and hyperactivity disorder. / Rizzo, Francesca; Nespoli, Ester; Abaei, Alireza; Bar-Gad, Izhar; Deelchand, Dinesh K.; Fegert, Jörg; Rasche, Volker; Hengerer, Bastian; Boeckers, Tobias M.

In: Frontiers in Neurology, Vol. 9, No. FEB, 59, 13.02.2018.

Research output: Contribution to journalArticle

Rizzo, Francesca ; Nespoli, Ester ; Abaei, Alireza ; Bar-Gad, Izhar ; Deelchand, Dinesh K. ; Fegert, Jörg ; Rasche, Volker ; Hengerer, Bastian ; Boeckers, Tobias M. / Aripiprazole selectively reduces motor tics in a young animal model for Tourette's syndrome and comorbid attention deficit and hyperactivity disorder. In: Frontiers in Neurology. 2018 ; Vol. 9, No. FEB.
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AU - Rizzo, Francesca

AU - Nespoli, Ester

AU - Abaei, Alireza

AU - Bar-Gad, Izhar

AU - Deelchand, Dinesh K.

AU - Fegert, Jörg

AU - Rasche, Volker

AU - Hengerer, Bastian

AU - Boeckers, Tobias M.

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KW - Tourette's syndrome

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