The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function

• Published in: Psychopharmacology Vol. 232; no. 21-22; pp. 3947 - 3966
• Main Authors: Kim, Chi Hun, Hvoslef-Eide, Martha, Nilsson, Simon R. O., Johnson, Mark R., Herbert, Bronwen R., Robbins, Trevor W., Saksida, Lisa M., Bussey, Timothy J., Mar, Adam C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2015; Springer; Springer Nature B.V
• Subjects: Animal cognition; Animals; Attention; Attention - drug effects; Biomedical and Life Sciences; Biomedicine; Care and treatment; Cholinesterase Inhibitors - pharmacology; Cognition; Conditioning, Operant - drug effects; Discrimination Learning - drug effects; Discrimination, Psychological - drug effects; Donepezil; Drug Evaluation, Preclinical; Humans; Indans - pharmacology; Male; Mental illness; Methods; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neurosciences; Nootropic Agents - pharmacology; Observations; Original Investigation; Perception; Pharmacology/Toxicology; Physiological aspects; Piperidines - pharmacology; Psychiatry; Psychoanalysis; Psychomotor Performance - drug effects; Psychopharmacology; Rodents; Species Specificity; Task analysis; Testing; Visual Perception - drug effects; Mouse; Continuous performance test; Touchscreen operant chamber; Donepezil; Mouse strain differences
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-4081-0

Rationale
Continuous 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.
Objectives
The 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.
Methods
C57BL/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.).
Results
C57BL/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.
Conclusions
rCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.