At a molecular level, balanced dopamine-glutamate interaction is mediated through functional interactions between dopamine D1 receptor (DRD1) and the NMDA glutamate receptors in postsynaptic neurons. DRD1 activation enhances NMDA receptor activity and induces rapid trafficking of intracellular NMDA receptors to the postsynaptic density. Post-synaptic density protein 95 (PSD-95, DLG4) interacts with NMDA receptors via NR2 subunits and may help to localize these receptors to the synapse.10,11 PSD-95 also interacts with DRD1 via the N-terminus of PSD-95 and the C-terminus of DRD1 to regulate DRD1 trafficking.12 In addition to PSD-95, HOMER proteins (HOMER1-3) are also present at the postsynaptic density and play a critical role in glutamatergic transmission and also complex with PSD-95 by the Shank proteins.13–15 Animal models have provided significant evidence in strong support of a role of HOMER and PSD-95 proteins in addiction disorders,16–18 but no study has yet evaluated genetic variants in these genes in relation to opiate abuse. Moreover, despite the prevailing hypotheses regarding aberrant striatal synaptic plasticity and disturbance of HOMER and PSD-95 in addiction disorders, no information is available about their expression in the human striatum of drug abusers.
