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- Title
A New Three-Hit Mouse Model of Neurodevelopmental Disorder with Cognitive Impairments and Persistent Sociability Deficits.
- Authors
Mouffok, Imane; Lahogue, Caroline; Cailly, Thomas; Freret, Thomas; Bouet, Valentine; Boulouard, Michel
- Abstract
Background/Objectives: Cognitive deficits and negative symptoms associated with schizophrenia are poorly managed by current antipsychotics. In order to develop effective treatments, refining animal models of neurodevelopmental disorders is essential. Methods: To address their multifactorial etiology, we developed a new three-hit mouse model based on the hypoglutamatergic hypothesis of the pathology combined with early stress, offering strong construct validity. Thus, a genetic susceptibility (serine racemase deletion) was associated with an early environmental stress (24 h maternal separation at 9 days of age) and a further pharmacological treatment with phencyclidine (PCP, a glutamate receptor antagonist treatment, 10 mg/kg/day, from 8 to 10 weeks of age). The face validity of this model was assessed in female mice 1 and 6 weeks after the end of PCP treatment by a set of behavioral experiments investigating positive- and negative-like symptoms and cognitive deficits. Results: Our results showed that the three-hit mice displayed persistent hyperlocomotion (positive-like symptoms) and social behavior impairment deficits (negative-like symptoms) but non-persistent spatial working memory deficits (cognitive symptoms). Conclusions: Our work confirms the usefulness of a three-hit combination to model, particularly for negative-like symptoms associated with schizophrenia and other psychiatric disorders. The model therefore gathers powerful construct and face validities and supports an involvement of glutamate dysfunction in behavioral symptoms.
- Subjects
EXCITATORY amino acid antagonists; MEMORY disorders; MENTAL illness; COGNITION disorders; TEST validity
- Publication
Brain Sciences (2076-3425), 2024, Vol 14, Issue 12, p1281
- ISSN
2076-3425
- Publication type
Academic Journal
- DOI
10.3390/brainsci14121281