Comparative Evaluation of Behavioral Tests Efficiency in Learning of Dopamine Transporter Knockout Rats

Objective: The dopamine transporter knockout (DAT-KO) rats are an optimal model for studying attention deficit hyperactivity disorder (ADHD). This model has tremendous potential for biotranslational research to guide the development of new approaches to ameliorating the symptoms of human neuropsychiatric disorders. However, studies of learning and memory in DAT-KO rats have difficulties and limitations due to their pronounced hyperactivity. The aim of this study was to reveal the most effective behavioral tasks for experiments at DAT-KO rats. We analyzed the dynamics of tracks in different mazes as an indicator of task successful learning Methods: During long-term experiments we tested several behavioral paradigms such as 8-Arm Radial Maze, Hebb-Williams maze, T-maze, Red Box apparatus. The comparison of learning differences of DAT-KO and WT rats was made. Results and Discussion: DAT-KO rats were able to learn in all selected maze types, but they learned significantly less efficiently than WT rats. DAT-KO rats also showed perseverative patterns, such as repeatedly entering error zones and returning to previously visited areas. However, in experiments involving manipulative behavioral tasks, this perseverative activity was useful for successful task performance. The configuration of the tracks during exploration of the maze also differed between the two groups of animals, reflecting the rate and efficiency of learning. Conclusions: Choosing and developing the most adequate methodological approaches can help to evaluate the novel pharmacological approaches to ADHD treatment. Selecting appropriate behavioral tests for hyperactive rats is also essential for creating training techniques for patients with ADHD.