Preliminary studies of human cortical 5-HT2 receptors and their involvement in schizophrenia and neuroleptic drug action.

It is well established that neuroleptic drugs are antagonists of brain dopamine receptors. The role of the reported increase in dopamine receptors (measured as 3H-spiperone binding sites) in post-mortem brain tissue from patients with schizophrenia in the aetiology of the disease is, however, unclear. We have found this increase only in chronically neuroleptic-treated patients, indicating that the increase is probably due to this neuroleptic treatment. Many neuroleptic drugs have a high affinity for a subgroup of 5-hydroxytryptamine receptors, which have also been implicated in schizophrenia. Using the specific ligand 3H-ketanserin, we find that certain neuroleptics have a higher affinity for these 5-HT2 receptors than for the dopamine D2 site. Although changes in these receptors have been reported in schizophrenic brain tissue we have been unable to find any difference in receptor density in cortical tissue from schizophrenics and control subjects.