Metabolic alterations in the prefrontal and cingulate cortices are related to behavioral deficits in a rodent model of attention-deficit hyperactivity disorder

Abstract

Rats with a deficit in selective attention accompanied by impulsivity can be identified using a five-choice serial reaction time task (5-CSRT) and have been proposed to represent a rodent model of attention-deficit hyperactivity disorder (ADHD). The aim of the present study was to investigate which brain areas are important for visuospatial attention and to test the specific hypothesis that dysfunction of the frontal cortex is related to the behavioral deficits observed in poorly performing rats. Therefore, [14C]deoxyglucose (DG) uptake, an index of brain metabolic activity, was measured during the performance of a 5-CSRT task in two populations of rats (poorly and well-performing rats) to study the relationships between the regional brain activity and behavioral output. While performing a 5-CSRT task, poorly performing rats exhibited lower DG uptake in the cingulate and ventrolateral orbital cortices than did well-performing rats,. Moreover, there was a positive correlation between choice accuracy and DG uptake in several areas, especially in the frontal and parietal regions, whereas there was an inverse correlation between the percentage of premature responses and DG uptake in the ventrolateral orbital and cingulate cortices. These results, which demonstrated that the poorly performing rats exhibited metabolic dysfunction in the cingulate and prefrontal cortices, provide a basis for the face validity of the rodent model of ADHD. Moreover, they suggest that the neural network of attention in rats is remarkably analogous to that described in primates.