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

Nilsson, Simon R.O.; Heath, Christopher J.; Takillah, Samir; Didienne, Steve; Fejgin, Kim; Nielsen, Vibeke; Nielsen, Jacob; Saksida, Lisa M.; Mariani, Jean; Faure, Philippe; Didriksen, Michael; Robbins, Trevor W.; Bussey, Timothy J. and Mar, Adam C. (2018). Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine. Translational Psychiatry, 8, article no. 247.

DOI: https://doi.org/10.1038/s41398-018-0295-3

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 (0-1.0mg/kg, i.p.) dose-dependently improved d’ in Df(h22q11)/+ mice whereas the highest dose of modafinil (40mg/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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