Adenosine A2a receptor/dopamine D2 receptor hetero-oligomerization: a hypothesis that may explain behavioral sensitization to psychostimulants and schizophrenia.

The mechanisms underlying psychostimulant-induced behavioral sensitization and schizophrenia are yet to be fully elucidated. Evidence suggests that the dopamine D2 receptor (DRD2) as well as other neurotransmitter system receptors may be involved in the two conditions, and previous reports have hypothesized that oligomerization of dopamine receptors and analogs from other neurotransmitter systems may underlie the mechanism responsible. This paper describes findings which show co-localization of DRD2 and the adenosine A2a receptor (A2aAR) in the striatum, interaction between the two receptors and A2aAR/DRD2 hetero-oligomerization in the neuronal cell. The possibility that A2aAR/DRD2 hetero-oligomerization may be involved in the development of psychostimulant-induced behavioral sensitization or the pathogenesis of schizophrenia is explored. A2aAR/DRD2 hetero-oligomerization can enhance dopaminergic function, resulting in an increased behavioral response to psychostimulants or the development of psychotic symptoms. Receptor oligomerization can affect receptor degradation, which may affect the persistence of behavioral sensitization or psychotic symptoms. The proposed A2aAR/DRD2 hetero-oligomerization model may suggest new directions in the understanding and treatment of schizophrenia.