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Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine

Abstract : The 22q11.2 deletion syndrome (22q11.2DS) confers high risk of neurodevelopmental disorders such as schizophrenia and attention-deficit hyperactivity disorder. These disorders are associated with attentional impairment, the remediation of which is important for successful therapeutic intervention. We assessed a 22q11.2DS mouse model (Df(h22q11)/+) on a touchscreen rodent continuous performance test (rCPT) of attention and executive function that is analogous to human CPT procedures. Relative to wild-type littermates, Df(h22q11)/+ male mice showed impaired attentional performance as shown by decreased correct response ratio (hit rate) and a reduced ability to discriminate target stimuli from non-target stimuli (discrimination sensitivity, or d’). The Df(h22q11)/+ model exhibited decreased prefrontal cortical-hippocampal oscillatory synchrony within multiple frequency ranges during quiet wakefulness, which may represent a biomarker of cognitive dysfunction. The stimulant amphetamine (0–1.0 mg/kg, i.p.) dose-dependently improved d’ in Df(h22q11)/+ mice whereas the highest dose of modafinil (40 mg/kg, i.p.) exacerbated their d’ impairment. This is the first report to directly implicate attentional impairment in a 22q11.2DS mouse model, mirroring a key endophenotype of the human disorder. The capacity of the rCPT to detect performance impairments in the 22q11.2DS mouse model, and improvement following psychostimulant-treatment, highlights the utility and translational potential of the Df(h22q11)/+ model and this automated behavioral procedure.
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Submitted on : Friday, November 16, 2018 - 11:56:47 AM
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Simon Nilsson, Christopher Heath, Samir Takillah, Steve Didienne, Kim Fejgin, et al.. Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine. Translational Psychiatry, Nature Pub. Group, 2018, 8 (1), pp.247. ⟨10.1038/s41398-018-0295-3⟩. ⟨hal-01924805⟩

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