Non-uniform blockade of intrastriatal D(2)/D(3) receptors by risperidone and amisulpride

JM Stone*, Rodrigo Affonseca Bressan, K Erlandsson, PJ Ell, LS Pilowsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Rationale: Atypical antipsychotic drugs have been shown to preferentially affect extrastriatal (mesolimbic) D(2)/D(3) receptors over those within the striatum (nigrostriatal). The striatum does not contain exclusively nigrostriatal dopamine tracts, however. The caudate nucleus and ventral parts of the striatum primarily contain limbic and associative dopamine pathways more relevant to psychosis. Objectives: We tested the hypothesis that two pharmacologically distinct atypical antipsychotic drugs, amisulpride and risperidone, would preferentially occupy of D(2)/D(3) dopamine receptors in limbic and associative regions of the striatum. Methods: Eight amisulpride-treated patients, six risperidone-treated patients and six age- and sex-matched healthy controls were recruited. Dynamic SPET studies were performed after bolus injection of [(123)I]epidepride. Binding potential (BP) images were generated using a modified Logan method and aligned between subjects. Regions of interest (ROIs) were placed around head of caudate and putamen bilaterally on an average BP map derived from aligned control images. These ROIs were then applied user-independently to the BP maps for each subject to calculate BP for head of caudate and putamen. Mean occupancy of D(2)/D(3) receptors in each ROI was determined by reference to the drug-free healthy volunteer group. Occupancy values for head of caudate and putamen were compared using paired Student's t test. Results: D(2)/D(3) receptor occupancy was 42% in caudate and 31% in putamen for risperidone (t=5.9, df=11, p=0.0001) and 51% in caudate and 37% in putamen for amisulpride (t=11.1, df=15, p <0.0001). Conclusions: Amisulpride and risperidone both show selective occupancy for limbic and associative D(2)/D(3) receptors within the striatum.

Original languageEnglish
Pages (from-to)664-669
Number of pages6
JournalPsychopharmacology
Volume180
Issue number4
DOIs
Publication statusPublished - Aug 2005

Keywords

  • antipsychotic agents
  • atypical antipsychotic
  • neuroleptic
  • schizophrenia
  • D(2)
  • D(3)
  • dopamine
  • SPECT
  • photon emission tomography
  • [(123)I]epidepride
  • EMISSION-TOMOGRAPHY SPET
  • IN-VIVO
  • ANTIPSYCHOTIC-DRUGS
  • PARKINSONS-DISEASE
  • TREATED PATIENTS
  • BASAL GANGLIA
  • ATYPICAL ANTIPSYCHOTICS
  • LIMBIC SELECTIVITY
  • DOPAMINE-RECEPTORS
  • HUMAN-BRAIN

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