Route selection impairment and microglia activation in a rodent model of attention-deficit hyperactivity disorder.

Introduction: The ability to remember locations of objects and make spatial decisions is critical when navigating an environment. Such tasks, however, can be difficult for individuals with certain neurological conditions, such as attention deficit hyperactivity disorder (ADHD). The traveling salesperson problem (TSP), a naturalistic spatial foraging task, has been effectively used to examine these spatial navigational processes in rodents, as this optimization task requires subjects to identify the shortest route of travel between a certain number of targets in an open arena. Previous studies using the TSP task have found that rats with hippocampal or medial entorhinal cortex lesions are impaired on measures of spatial memory, but not spatial decision-making or route selection. Methods: The current study examined the performance of male and female spontaneously hypertensive rats (SHR), the most widely used rodent model of ADHD, relative to their control model, Wistar Kyoto (WKY) rats, on the TSP task. Results: Our behavioral findings suggest that both male and female SHRs have greater deficits in route selection compared to WKY rats, but they show intact performance on measures of spatial memory. We also examined microglia expression as a marker of neuroinflammation in the prefrontal cortex, hippocampus, and medial entorhinal cortex. SHRs had a greater percentage of hypertrophic microglia, indicating extended periods of inflammation or activation, in the infralimbic area of the prefrontal cortex and in the dentate gyrus. Within the dentate gyrus, the female SHRs showed an increased percentage of hypertrophic microglia compared to female WKY rats. Discussion: This study expands on existing literature within ADHD-model male and female rats by exploring their ability to effectively route optimize using a naturalistic task.