Abstract
RationaleContinuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer’s disease and schizophrenia. Common human CPTs require discrimination of sequentially presented, visually patterned ‘target’ and ‘non-target’ stimuli at a single location.ObjectivesThe aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer.MethodsC57BL/6J, DBA/2J and CD1 mice (n = 15–16/strain) were trained to baseline performance using four rCPT training stages. Then, probe tests assessed the effects of parameter changes on task performance: stimulus size, duration, contrast, probability, inter-trial interval or inclusion of flanker distractors. rCPT performance was also evaluated following acute administration of donepezil (0–3 mg/kg, i.p.).ResultsC57BL/6J and DBA/2J mice showed similar acquisition rates and final baseline performance following rCPT training. On probe tests, rCPT performance of both strains was sensitive to alteration of visual and/or attentional demands (stimulus size, duration, contrast, rate, flanker distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing sensitivity (d′) across the 45-min session, (2) reduced performance on probes where the appearance of stimuli or adjacent areas were changed (size, contrast, flanking distractors) and (3) larger dose- and stimulus duration-dependent changes in performance following donepezil administration. In contrast, CD1 mice failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks.ConclusionsrCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.
Highlights
The continuous performance test (CPT) has been widely used to assess deficits in attentional function in many neurodegenerative and neuropsychiatric disorders including Alzheimer’s disease (Perry and Hodges 1999; Stopford et al 2012) and schizophrenia (Cornblatt et al 1989; Cornblatt and Malhotra 2001)
There were no strain differences between C57, DBA/ 2J (DBA) or CD1 mice in the number of sessions taken to reach the criterion on rCPT training stage 1 or 2: stage 1 (χ2(2)=0.53, p=0.77, min 2, max 10), stage 2 (χ2(2)=3.10, p=0.21, min 1, max 4)
Testing of CD1 on the rCPT was discontinued and the study focussed on C57 and DBA strains
Summary
The continuous performance test (CPT) has been widely used to assess deficits in attentional function in many neurodegenerative and neuropsychiatric disorders including Alzheimer’s disease (Perry and Hodges 1999; Stopford et al 2012) and schizophrenia (Cornblatt et al 1989; Cornblatt and Malhotra 2001). In the original version (X-CPT), Rosvold et al (1956) asked subjects to monitor a sequentially presented series of letters on a monitor and to respond only when the letter (‘X’) appeared. Numerous versions of CPT have been introduced that vary cognitive load such as working memory and/or perceptual load (e.g. AX-CPT: Rosvold et al (1956), ‘identical pairs’ CPT: Cornblatt et al (1989), ‘noisy stimulus’ CPT: Nuechterlein et al (1983)). To successfully translate results from preclinical work to the clinic, comparable and sensitive tests in animals are essential. To this end, devising attentional tasks with analogous features in both humans and animals can help maximise the chances of successful translation across species in preclinical and clinical stages of drug development (Nuechterlein et al 2009; Lustig et al 2013). Mouse versions of cognitive tests are important, as many disease models are currently available only in mice (Papaleo et al 2012; Webster et al 2014)
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