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Published on: December 24, 2013
The Sapap3-/- mouse reconsidered as a comorbid model expressing a spectrum of pathological repetitive behaviours
Hugues Lamothe1,2, Christiane Schreiweis1, Lizbeth Sirenia Mondragón-González1
1Team "Neurophysiology of Repetitive Behaviours", Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
Abstract:
Symptom comorbidity is present amongst neuropsychiatric disorders with repetitive behaviours, complicating clinical diagnosis and impeding appropriate treatments. This is of particular importance for obsessive-compulsive disorder (OCD) and Tourette syndrome. Here, we meticulously analysed the behaviour of Sapap3 knockout mice, the recent rodent model predominantly used to study compulsive-like behaviours, and found that its behaviour is more complex than originally and persistently described. Indeed, we detected previously unreported elements of distinct pathologically repetitive behaviours, which do not form part of rodent syntactic cephalo-caudal self-grooming. These repetitive behaviours include sudden, rapid body and head/body twitches, resembling tic-like movements. We also observed that another type of repetitive behaviour, aberrant hindpaw scratching, might be responsible for the flagship-like skin lesions of this mouse model. In order to characterise the symptomatological nature of observed repetitive behaviours, we pharmacologically challenged these phenotypes by systemic aripiprazole administration, a first-line treatment for tic-like symptoms in Tourette syndrome and trichotillomania. A single treatment of aripiprazole significantly reduced the number of head/body twitches, scratching, and single-phase grooming, but not syntactic grooming events. These observations are in line with the high comorbidity of tic- and compulsive-like symptoms in Tourette, OCD and trichotillomania patients.
Insights
Sapap3 knockout mice exhibit complex repetitive behaviors beyond grooming, including tic-like twitches and scratching. Aripiprazole treatment reduced these abnormal movements, suggesting shared mechanisms with Tourette syndrome and OCD.
Area of Science:
- Neuroscience
- Behavioral Science
- Pharmacology
Background:
- Neuropsychiatric disorders like obsessive-compulsive disorder (OCD) and Tourette syndrome often present with comorbid repetitive behaviors, complicating diagnosis and treatment.
- The Sapap3 knockout mouse is a key model for studying compulsive-like behaviors, but its behavioral repertoire may be more complex than previously understood.
Purpose of the Study:
- To comprehensively analyze the behavioral phenotypes of Sapap3 knockout mice, identifying previously unreported repetitive behaviors.
- To investigate the pharmacological response of these behaviors to aripiprazole, a medication used for tic-like symptoms.
Main Methods:
- Detailed behavioral analysis of Sapap3 knockout mice to identify distinct repetitive behaviors.
- Pharmacological intervention using systemic aripiprazole administration.
- Assessment of aripiprazole's effect on specific repetitive behaviors, including twitches, scratching, and grooming.
Main Results:
- Sapap3 knockout mice display pathological repetitive behaviors not part of normal grooming, such as head/body twitches and aberrant hindpaw scratching.
- Aripiprazole significantly decreased the frequency of head/body twitches, scratching, and single-phase grooming.
- Syntactic grooming events were not affected by aripiprazole treatment.
Conclusions:
- The Sapap3 knockout mouse model exhibits a broader range of repetitive behaviors than previously recognized, including tic-like and compulsive-like actions.
- Pharmacological modulation with aripiprazole suggests shared neurobiological underpinnings between these behaviors and those seen in Tourette syndrome, OCD, and trichotillomania.
- These findings support the utility of the Sapap3 knockout mouse in modeling complex symptom comorbidities observed in human neuropsychiatric disorders.
