Dopamine receptor homooligomers and heterooligomers in schizophrenia

Over the past two decades the dopamine D2 receptor has been undoubtedly the most widely studied dopamine receptor for the therapeutic treatment of schizophrenia, as the majority of antipsychotics exhibit antagonism at this receptor. However, the cognitive symptoms of the disorder are mostly resistant to the majority of available antipsychotic treatments and, as a result, there is a critical need to develop novel therapies that ameliorate all symptoms. The recognition that dopamine receptors, such as all G protein-coupled receptors (GPCRs), exist as oligomeric complexes has provided new avenues for drug design in the search for novel therapies. Furthermore, that it is now known that dopamine receptors can form heteromers, such as the dopamine D1-D2 receptor heteromer, with pharmacology and function distinct from its constituent receptors, has significantly expanded the range of potential drug targets. The aim of this review is to discuss the therapeutic relevance of these dopamine receptor oligomers to schizophrenia and to address the potential value of dopamine receptor heteromers in the search for new therapeutic strategies.