STAM1-deficient mice exhibit an attention-deficit/hyperactivity disorder-like phenotype.

Abstract

Despite recent abundant studies on animal models of attention-deficit/hyperactivity disorder (ADHD), a complete model remains unestablished. In this study, we investigated the potential of STAM1-deficient mice as a new animal model for ADHD. STAM1-deficient mice escaped from a high platform significantly faster than wild-type mice, indicating ADHD-like impulsivity. Low anxiety-like behavior in STAM1-deficient mice was also confirmed in an elevated plus maze and light and dark compartment test. STAM1-deficient mice also showed a slight increase in locomotor activity, an indicator of ADHD-like hyperactivity, compared to wild-type mice. The ADHD therapeutic agent atomoxetine ameliorated ADHD-like impulsivity observed in STAM1-deficient mice; STAM1-deficient mice treated with the dopamine Dreceptor antagonist clozapine, but not the dopamine Dreceptor antagonist haloperidol, showed reduced ADHD-like impulsivity. Additionally, STAM1-deficient mice showed decreased serotonin levels in the prefrontal cortex and hypothalamus, along with reduced dopamine levels in the caudate putamen. These results indicate that STAM1-deficient mice show ADHD-like symptoms, suggesting the possibility of a new ADHD animal model. Moreover, clozapine may be a new therapeutic agent for ADHD.