Dopamine D2-like sites in schizophrenia, but not in Alzheimer's, Huntington's, or control brains, for [3H]benzquinoline

Philip Seeman, Hong Chang Guan, José Nobrega, Dilshad Jiwa, Rudolph Markstein, Ja Hyun Balk, Roberto Picetti, Emiliana Borrelli, Hubert H.M. Van Tol

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Although the basis of schizophrenia is not known, evidence indicates a possible overactivity of dopamine pathways. In order to detect any new dopamine receptor-like sites which may be altered in schizophrenia, the present study used a new radioligand, a [3H]benzo[g]quinoline. The receptors were labelled by this ligand in the presence of other drugs to block the known dopamine D1, D2, D3, or D5 receptors (no D4-selective ligands are available to block D4). Using this method, we found that schizophrenia brain striata had elevated levels of a D2-1ike site not detected in control human postmortem brains or in Alzheimer's, Huntington's, or Parkinson's disease brains. The ligand acted as an agonist at this D2-1ike site, because binding was abolished by guanine nucleotide. The binding of the ligand to the D4 receptor, however, was not sensitive to guanine nucleotide. The site differed from D2 itself, because S- and R-sulpiride were equally potent at the D2- 1ike site. The D2-like sites were present in rat and mouse brain but were absent in brain slices from transgenic mice where D2 had been knocked out. The abundance of the receptor was not related to premortem use of antipsychotic drugs. Future research should examine the biochemical differences between the D2 dopamine receptor and these D2-like sites in schizophrenia.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalSynapse
Volume25
Issue number2
DOIs
Publication statusPublished - 1997 Feb
Externally publishedYes

Keywords

  • D4 dopamine receptor
  • Huntington's disease
  • Sandoz GLC 756 dopamine agonist
  • dopamine D2 knockout
  • dopamine D2-like receptor
  • schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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