Recent clinical studies have shown that serotonin–norepinephrine reuptake inhibitors such as venlafaxine and duloxetine are effective against symptoms of attention–deficit/hyperactivity disorder such as inattention, oppositionality, and hyperactivity. We have recently found that these serotonin–norepinephrine reuptake inhibitors, like methylphenidate, reduced the hyperactivity in spontaneously hypertensive rats (SHR), an animal model of attention–deficit/hyperactivity disorder. The present study investigated whether the α2-adrenoceptor and the dopamine-D1 receptor are involved in the behavioral effects of methylphenidate and venlafaxine in SHR. Adolescent male SHR showed greater horizontal locomotion in a familiar open field than male Wistar Kyoto and Wistar rats, and methylphenidate (0.3 mg/kg) and venlafaxine (30 mg/kg) reduced horizontal locomotion in SHR, but not Wistar Kyoto or Wistar rats. The effects of methylphenidate and venlafaxine were blocked by idazoxan (an α2-adrenoceptor antagonist), but not by SCH23390 (a dopamine-D1 receptor antagonist). These findings suggest that the α2-adrenoceptor plays a key role in the effects of methylphenidate and venlafaxine on enhanced locomotion in SHR.