DOPAMINE D2-LIKE SITES IN SCHIZOPHRENIA, BUT NOT IN ALZHEIMERS, HUNTINGTONS, OR CONTROL BRAINS, FOR [H-3] BENZQUINOLINE

Although the basis of schizophrenia is not known, evidence indicates a possible overactivity of dopamine pathways. In order to detect any ne w dopamine receptor-like sites which may be altered in schizophrenia, the present study used a new radioligand, a [H-3]benzo[g]quinoline. Th e receptors were labelled by this ligand in the presence of other drug s to block the known dopamine D1, D2, D3, or D5 receptors (no D4-selec tive ligands are available to block D4). Using this method, we found t hat schizophrenia brain striata had elevated levels of a DB-like site not detected in control human postmortem brains or in Alzheimer's, Hun tington's, or Parkinson's disease brains. The ligand acted as an agoni st at this DB-like site, because binding was abolished by guanine nucl eotide. The binding of the ligand to the D4 receptor, however, was not sensitive to guanine nucleotide. The site differed from D2 itself, be cause S- and R-sulpiride were equally potent at the DB-like site. The DB-like sites were present in rat and mouse brain but were absent in b rain slices from transgenic mice where D2 had been knocked out. The ab undance of the receptor was not related to premortem use of antipsycho tic drugs. Future research should examine the biochemical differences between the D2 dopamine receptor and these DB-like sites in schizophre nia. (C) 1997 Wiley-Liss, Inc.