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Transl Psychiatry. 2018 Nov 14;8(1):247. doi: 10.1038/s41398-018-0295-3.

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

Nilsson SRO1,2,3,4, Heath CJ5, Takillah S6,7,8,9,10, Didienne S8, Fejgin K11, Nielsen V11, Nielsen J11, Saksida LM1,2,12,13,14, Mariani J9,10, Faure P7, Didriksen M11, Robbins TW1,2, Bussey TJ1,2,12,13,14, Mar AC15,16.

Author information

1
Department of Psychology, University of Cambridge, Cambridge, UK.
2
MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
3
Neuroscience Institute, New York University Medical Center, New York, NY, USA.
4
Department of Neuroscience and Physiology, School of Medicine, New York University, New York, NY, USA.
5
School of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, UK.
6
Fatigue and Vigilance team, Neuroscience and Operational Constraints Department, French Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
7
VIFASOM team (EA 7330), Paris Descartes University, Sorbonne Paris Cité, Hôtel Dieu, Paris, France.
8
Sorbonne Universités, Université Pierre et Marie Curie (UPMC), CNRS, INSERM, U1130, Institut de Biologie Paris Seine (IBPS), UMR 8246 Neuroscience Paris Seine (NPS), Team Neurophysiology and Behavior, Paris, France.
9
Sorbonne Universités, Université Pierre et Marie Curie (UPMC), CNRS, Institut de Biologie Paris Seine (IBPS), UMR 8256 Biological adaptation and ageing (B2A), Team Brain Development, Repair and Ageing, Paris, France.
10
APHP Hôpital, DHU Fast, Institut de la Longévité, Ivry-Sur-Seine, France.
11
H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Copenhagen, Denmark.
12
Molecular Medicine Research Group, Robarts Research Institute & Department of Physiology, Western University, London, ON, Canada.
13
Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
14
The Brain and Mind Institute, Western University, London, ON, Canada.
15
Neuroscience Institute, New York University Medical Center, New York, NY, USA. Adam.Mar@nyumc.org.
16
Department of Neuroscience and Physiology, School of Medicine, New York University, New York, NY, USA. Adam.Mar@nyumc.org.

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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