SUMMARY

Functional and morphological studies in children affected by Attention Deficit Hyper-activity Disorder (ADHD) suggest a prefrontal cortex (PFc) dysfunction. This cortical region is regulated by subcortical systems including nor-adrenergic (NEergic), dopaminergic (DAergic), cholinergic, serotonergic, and histaminergic path-ways. A wealth of data in humans and in animal models demonstrates altered dopamine (DA) regulation. Drugs that modulate norepinephrine (NE) transmission are also effective in ADHD patients, thus leading to the hypothesis of a NEergic disorder. This review covers the regulation of PFc functions by NE and the interaction between the NE and DA systems, as suggested by pharmacological, electrophysio-logical, morphological, and gene knock out (KO) studies. A negative feedback between NE and DA neurons emerges from KO studies because KO mice showing increased (NE transporter (NET) KO) or decreased (DBH and VMAT2 KO) NE levels are respectively associated with lower and higher DA levels. Locomotor activity can be generally predicted by the DA level, whereas sensitivity to amphetamines is by NE/DA balance