Sodium-dependent dopamine transporter and Sodium-dependent noradrenaline transporter (DAT/NET)

The Dopamine Transporter (DAT) and Norepinephrine Transporter (NET) are integral membrane proteins belonging to the solute carrier family 6 (SLC6) that regulate the intensity and duration of monoaminergic signaling [2, 6]. DAT is primarily responsible for the reuptake of dopamine in the striatum, while NET mediates the reuptake of norepinephrine and, to a significant extent, dopamine in the prefrontal cortex [2, 7]. Together, these transporters maintain neurotransmitter homeostasis and are critical in modulating arousal, attention, and reward pathways [6]. Dysregulation of DAT and NET is implicated in various neuropsychiatric conditions, including attention deficit hyperactivity disorder (ADHD), depression, and Parkinson's disease [12, 18]. Pharmacological agents targeting both transporters, known as norepinephrine-dopamine reuptake inhibitors (NDRIs), are widely used to treat ADHD and depressive disorders by increasing synaptic availability of these catecholamines [5, 10]. Additionally, these transporters are the primary targets for several psychostimulants and drugs of abuse, which can lead to significant cardiovascular side effects and potential for addiction [11, 13].

Other names

SLC6A3SLC6A2DATNETDAT1NET1Sodium-dependent dopamine transporterSodium-dependent noradrenaline transporter

Inhibition of the reuptake of dopamine and norepinephrine from the synaptic cleft into the presynaptic neuron, thereby increasing the extracellular concentration of these neurotransmitters [6, 10].