The synergistic effects of Sp1 and MAO A on functions of glucocorticoid receptor (GR) and monoamine oxidase A (MAO A) were studied in attention-deficit hyperactivity disorder (ADHD) model animal spontaneously hypertensive rat (SHR), using dexamethasone (DEX) and mifepristone (RU486) as GR agonist and inhibitor, respectively. Locomotor activity and non-selective attention of SHR were evaluated by using open field test and lat maze. The expression levels of Sp1 and MAO A were determined by immunocytochemical staining after cell primary culture. After DEX treatment, the number of crossing grid (54.38±10.42), grooming (12.38±2.50), crossing the corner (59.88±9.09) and upright (52.13±15.33) were all less than that of control, while RU486 did not induce change of above behaviors. Meanwhile, the expression levels of Sp1 and MAO A in the hippocampus cell in the DEX group (74816.16±2327.20 and 65643.31±3881.68) were distinctly increased, and the RU486 group (44751.96±2982.23 and 45873.93±3726.63) were decreased (P<0.001). The expression levels in the prefrontal cortex were higher in DEX group than in control group (P<0.001), but RU486 group (56166.81±1625.73 and 36218.07±2912.10) were obviously lower than that of control group (P<0.05). This study showed GC can improve the spontaneous activity and non-selective attention of SHR effectively, indicating ADHD has abnormal function in HPA axis. GC can enhance the expression of Sp1 and MAO A in the neural cells by activating GR. Moreover, there is a positive correlation between Sp1 and MAOA. These findings suggest that the interaction between Sp1 and MAOA may involve in GR mediated pathogenesis of ADHD.