Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Nilsson, Simon; Heath, Christopher; Takillah, Samir; Didienne, Steve; Fejgin, Kim; Nielsen, Vibeke; Nielsen, Jacob; Saksida, Lisa; Mariani, Jean; Faure, Philippe; Didriksen, Michael; Robbins, Trevor; Bussey, Timothy; Mar, Adam
• Is Part Of: Translational psychiatry. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 14
• Publication Date: 2018-12
• Subjects: Psychiatry -- Research -- Periodicals; Neurosciences -- Research -- Periodicals; Psychiatry -- Periodicals; Neurosciences -- Periodicals; Translational Research -- Periodicals; Health Policy -- Periodicals; Public Health -- Periodicals; 616.89
• DOI: 10.1038/s41398-018-0295-3
• Languages: English
• ISSNs: 2158-3188

Abstract

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.