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

Autor: Nilsson SRO; Department of Psychology, University of Cambridge, Cambridge, UK.; MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.; Neuroscience Institute, New York University Medical Center, New York, NY, USA.; Department of Neuroscience and Physiology, School of Medicine, New York University, New York, NY, USA., Heath CJ; School of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, UK., Takillah S; Fatigue and Vigilance team, Neuroscience and Operational Constraints Department, French Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.; VIFASOM team (EA 7330), Paris Descartes University, Sorbonne Paris Cité, Hôtel Dieu, Paris, France.; 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.; 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.; APHP Hôpital, DHU Fast, Institut de la Longévité, Ivry-Sur-Seine, France., Didienne S; 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., Fejgin K; H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Copenhagen, Denmark., Nielsen V; H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Copenhagen, Denmark., Nielsen J; H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Copenhagen, Denmark., Saksida LM; Department of Psychology, University of Cambridge, Cambridge, UK.; MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.; Molecular Medicine Research Group, Robarts Research Institute & Department of Physiology, Western University, London, ON, Canada.; Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.; The Brain and Mind Institute, Western University, London, ON, Canada., Mariani J; 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.; APHP Hôpital, DHU Fast, Institut de la Longévité, Ivry-Sur-Seine, France., Faure P; VIFASOM team (EA 7330), Paris Descartes University, Sorbonne Paris Cité, Hôtel Dieu, Paris, France., Didriksen M; H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Copenhagen, Denmark., Robbins TW; Department of Psychology, University of Cambridge, Cambridge, UK.; MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK., Bussey TJ; Department of Psychology, University of Cambridge, Cambridge, UK.; MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.; Molecular Medicine Research Group, Robarts Research Institute & Department of Physiology, Western University, London, ON, Canada.; Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.; The Brain and Mind Institute, Western University, London, ON, Canada., Mar AC; Neuroscience Institute, New York University Medical Center, New York, NY, USA. Adam.Mar@nyumc.org.; Department of Neuroscience and Physiology, School of Medicine, New York University, New York, NY, USA. Adam.Mar@nyumc.org.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2018 Nov 14; Vol. 8 (1), pp. 247. Date of Electronic Publication: 2018 Nov 14.
DOI: 10.1038/s41398-018-0295-3
Abstrakt: 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.
Databáze: MEDLINE