DAT1

DAT1, commonly referring to the gene SLC6A3, encodes the dopamine transporter (DAT), a presynaptic membrane protein that reuptakes dopamine from the synaptic cleft. By transporting dopamine back into the neuron, DAT terminates dopaminergic signaling and helps regulate dopamine levels in brain circuits involved in movement, motivation, and reward. DAT is a member of the neurotransmitter:sodium symporter family and is predominantly expressed in dopaminergic neurons, with high density in the striatum, including the caudate nucleus and putamen, and notable presence in mesolimbic pathways.

The SLC6A3 gene is located on chromosome 5p15.3. A well-studied genetic feature is a variable number tandem repeat (VNTR) in the 3' untranslated region, with common alleles typically ranging from 9 to 11 repeats. Some studies have suggested that different VNTR alleles may influence DAT expression levels, but findings are heterogeneous across populations and study designs. Consequently, although associations between the DAT1 VNTR and neuropsychiatric traits such as attention-deficit/hyperactivity disorder (ADHD), addictions, and personality traits have been reported, evidence is not consistent enough to support a diagnostic role for DAT1, and no clinical test uses this variant as a sole predictor.

Functionally, DAT activity can be modulated by regulatory proteins and signaling pathways that affect transporter trafficking to and from the plasma membrane, altering uptake efficiency. Psychostimulant drugs, including cocaine, methylphenidate, and amphetamine, target DAT and alter extracellular dopamine levels, contributing to their pharmacological effects and reinforcing properties. DAT imaging using PET or SPECT ligands is used in research and clinical contexts to assess dopaminergic integrity in disorders such as Parkinson’s disease, where DAT density is reduced.