Hyperactivity, impulsivity, and inattention comprise the main clinical symptoms of attention deficit hyperactivity disorder (ADHD). The neuronal circuits mediating executive functions and motor control are modulated by dopamine and noradrenaline. Guanfacine, a selective α2A-adrenoceptor agonist, is prescribed for ADHD treatment [1]. The guanfacine therapeutic application has been proposed based on the results of animal studies and subsequently translated to human patients [2]. The dopamine transporter knockout (DAT–KO) rats present a valid model for ADHD [3]. The DAT-KO rats are hyperactive and deficient in spatial working memory [4]. However, the effects of guanfacine have not been tested on DAT-KO rats. The present study characterized the effects of guanfacine on spatial cognition in DAT-KO rats.