Dysregulation between dopamine and glutamate neural systems is a central hypothesis of addiction disorders. Balanced dopamine-glutamate interaction is mediated through several functional interactions, including a physical interaction between DLG4 and DRD1 within the postsynaptic density to regulate DRD1 trafficking.12 Interestingly, by studying three separate populations of opiate abusers, we found that polymorphisms of DRD1, DLG4 and HOMER1 were associated with opiate abuse. Also, a strong gene-gene interaction between HOMER1 and DRD1 with heroin abuse was revealed, whose demonstration was limited to Caucasian populations, highlighting a disturbance of interactions between glutamatergic-DRD1 pathways. Such interactions were also evident on the functional level given the differential DRD1 genotype dose relationship to HOMER1 expression in the striatum of control and heroin subjects.
