Raul R. Gainetdinov

Involvement of Dopamine Transporters in Psychiatric Disorders

The plasma membrane dopamine transporter (DAT) and the vesicular monoamine transporter (VMAT2) are key regulators of dopamine neurotransmission. DAT acts to terminate the actions of dopamine by rapidly removing dopamine from the synapse, while VMAT2 mediates loading of dopamine from the cytoplasm to vesicles for storage and subsequent release. Recent data from our laboratories and others’ suggest that perturbation of the tightly regulated balance between these two transporters alters dopamine function and may predispose the neuron to damage by a variety of insults. While the selective degeneration of DAT- and VMAT2- expressing dopamine nerve terminals in the striatum that leads to Parkinson’s disease is the most well known example, several other disorders may result or be exacerbated by the altered transporter function. Data from cell culture, knockout models, and human studies reveal that DAT and VMAT2 expression can predict the selective vulnerability of neuronal populations. Here, we review the role of DAT and VMAT2 in neurodegenerative disease and suggest how these findings can be applied to our understanding of psychiatric disorders.