Attention Deficit Hyperactivity Disorder (ADHD) causes impaired visuospatial working memory (VWM), which primarily maps to the prefrontal cortex. However, little is known about the synaptic processes underlying cognitive loss in ADHD, or those ultimately involved in the preventive effect observed through the clinical use of Atomoxetine (ATX). To investigate the plasticity underlying ADHD related cognitive loss, and that potentially involved in the preventive action of Atomoxetine, allocentric VWM was assessed, as well as the dendritic spine number and proportional density on pyramidal neurons in the prefrontal cerebral cortex layer III of neonatal 6-hydroxydopamine-lesioned rats. The effect of acute ATX treatment was also assessed at 28 days of age. 6-OHDA induced lesions produced increased motor activity and a loss of VWM, concomitant with a reduction in thin spine density. ATX administration reversed cognitive loss, in conjunction with a decrease in thin spines and an increase in mushroom spines. A reduction in the proportion of spines involved in learning in hyperactive animals could account for the loss in cognitive function observed. Considering thin spine density was also reduced after ATX administration, we hypothesized that the restoration in cognitive function recorded could be brought about by an increase in memory related mushroom spines.Copyright © 2018 Elsevier Inc. All rights reserved.