Attention Deficit Hyperactivity Disorder (ADHD) is the most common psychiatric disorder reported particularly in children. Long-term use of antipsychotic drugs used in the treatment of ADHD has been shown to exert toxic effects on the brain. However, not enough research has been carried out on the neurotoxic effects of these drugs on the brain tissue. Atomoxetine (ATX) is the most widely used antipsychotic drug that has gained approval for ADHD treatment. The present study aims to determine the damage induced by long-term use of three different doses of ATX in the brain tissue of experimental rats. 24 rats were divided into Control group (0.5 mL saline), Group 2 (0.5 mg/mL ATX), Group 3 (1.0 mg/mL ATX), and Group 4 (2.0 mg/mL ATX), each group having 6 members. Their brain tissues were taken for stereological, histological, and nuclear factor kappa-B (NF-kB) protein expression analysis. ATX was determined to have caused a few alterations in the brain tissue, such as disruption in the endothelial epithelium of capillaries, a couple of large astrocyte nuclei, and mitotic astrocytes. Moreover, a significant difference was observed in Group 4 compared to Control Group in terms of astrocyte counts in the brain sections. As for Groups 3 and 4, there were differences in terms of oligodendrocyte counts in the incisions cultivated from the brain tissues of the animals. On the other hand, NF-kB positive astrocytes of Groups 3 and 4 differed significantly from those of Control and Group 2. The results of molecular dockings of the present study are in line with the in-vivo results. Therefore, it was concluded that the higher the dose of ATX was, the more damage the brain tissue sustained. (c) 2020 Elsevier Inc. All rights reserved.