Adenosinergic system and nucleoside transporters in attention deficit hyperactivity disorder: Current findings

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high heterogeneity that can affect individuals of any age. It is characterized by three main symptoms: inattention, hyperactivity, and impulsivity. These neurobehavioral alterations and neurochemical and pharmacological findings are mainly attributed to unbalanced catecholaminergic signaling, especially involving dopaminergic pathways within prefrontal and striatal areas. Dopamine receptors and transporters are not solely implicated in this imbalance, as evidence indicates that the dopaminergic signaling is modulated by adenosine activity. To this extent, alterations in adenosinergic signaling are probably involved in ADHD. Here, we review the current knowledge about adenosine's role in the modulation of chemical, behavioral and cognitive parameters of ADHD, especially regarding dopaminergic signaling. Current literature usually links adenosine receptors signaling to the dopaminergic imbalance found in ADHD, but there is evidence that equilibrative nucleoside transporters (ENTs) could also be implicated as players in dopaminergic signaling alterations seen in ADHD, since their involvement in other neurobehavioral impairments.