In some cases, it has been shown that the heterodimer in question was indeed important in a given pathological situation, whereby either its density is increased, such as D1–D2 in depression, the reciprocal allosteric modulation of protomers is important (as in case of adenosine A2A and dopamine D2 receptors), or the specific location of the heterodimer would allow for the selective modulation of nociceptive stimuli (as in the case of the opioid system). This evidence concerns the gene DRD2 and depressive symptom measurement.