EN
Attention, its executive function in particular, is regulated by the dopaminergic (DA) system. Dopamine transporter (DAT), regulating DA neurotransmission, likely plays a role in controlling the influence of DA in cognitive processes. We examined the role of DAT in attention in mice and humans. Mice with DAT gene genetically deleted (DAT+/- heterozygotes) were compared with the wild type (WT) mice in several tests measuring attention. The effect of DAT inhibition was examined in mice submitted to repeated administration of selective DAT inhibitor – GBR 12909 and tested after 10 days of withdrawal. Locomotor activity and non-selective attention were tested in a Làt-maze, while attentional set-shifting, associative and reversal learning – in Attentional Set-Shifitng task (ASST). DAT level in the striatum was assessed using DAT immunohistochemistry. Neuronal activity in medial prefrontal cortex (mPFC) during ASST was visualized with the egr-1 and egr-2 immunohistochemistry and with [14C]-2-deoxyglucose autoradiography. Results have shown that DAT+/- mice had significantly higher scores of locomotor activity in comparison with WT mice. Heterozygotes did not differ from WT mice in respect of nonselective attention and associative learning measures. However, they were significantly impaired in more demanding tasks that tax the executive control function of attention. Also, neuronal activity level in mPFC of DAT+/- mice was significantly lower when compared with WT mice. These observations correspond well with behavioral results of children with attention deficit hyperactivity disorder (ADHD) examined in Attention Network Test (ANT), Sustained Attention to Response Task (SART) and in Test of Everyday Attention for Children (TEA-Ch) which revealed substantial deficits in executive function of attention. Measures of attention evaluated in attentional tests were analyzed in terms of relation with DAT1 gene polymorphisms. National Science Centre Grant 2011/01/D/NZ4/04958.