Abstract
Objective: In the framework of a larger project aiming to test putative cognitive enhancer drugs in a system with improved translational validity, we established a rodent test battery, where different, clinically relevant cognitive domains were investigated in the same animal population. The aim of the current study was to check whether performances in the different tasks representing different cognitive functions are assay-specific or may originate in an underlying general learning ability factor. Methods: In the experiments 36 Long-Evans and 36 Lister Hooded rats were used. The test battery covered the following cognitive domains: attention and impulsivity (measured in the 5-choice serial reaction time task), spatial memory (Morris water-maze), social cognition (cooperation task), cognitive flexibility (attentional set shifting test), recognition memory (novel object recognition) and episodic memory (water-maze based assay). The outcome variables were analyzed by correlation analysis and principal component analysis (PCA). The datasets consisted of variables measuring learning speed and performance in the paradigms. From the raw variables composite variables were created for each assay, then from these variables a composite score was calculated describing the overall performance of each individual in the test battery. Results: Correlations were only found among the raw variables characterizing the same assay but not among variables belonging to different tests or among the composite variables. The PCAs did not reduce the dimensionality of the raw or composite datasets. Graphical analysis showed variable performance of the animals in the applied tests. Conclusions: The results suggests the assay outcomes (learning performance) in the system are based on independent cognitive domains.
Highlights
Diseases of the brain pose the greatest health care challenge of the near future [1]
In Lister Hooded (LH) rats, correlations were found only between those variables that belonged to the same behavioral task
Similar pattern can be observed in LE rats, but in this dataset significant correlation was detected between the number of rewards collected in the cooperation task and time spent in the open arm in the elevated plus-maze (EPM) test (r = 0.49) (Fig. 2)
Summary
Diseases of the brain pose the greatest health care challenge of the near future [1]. The high unmet medical need has continuously stimulated the development of novel drugs, in the last 18 years none of them passed the clinical trials, in most cases because of lack of efficacy This failure suggests that the preclinical behavioral cognitive assays applied in drug development have low predictive value [2,3,4,5]. To mimic further the human circumstances, namely, the cognitive life experience of the subjects, the various learning tasks are taught to the same cohort of rats thereby a population with “widespread knowledge” is created This population may be transformed to various “patient populations” by applying distinct impairing methods and putative cognitive enhancers can subsequently be tested in these different “patient populations” [3]
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