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

TY - JOUR

T1 - Non-uniform blockade of intrastriatal D(2)/D(3) receptors by risperidone and amisulpride

AU - Stone, JM

AU - Bressan, Rodrigo Affonseca

AU - Erlandsson, K

AU - Ell, PJ

AU - Pilowsky, LS

PY - 2005/8

Y1 - 2005/8

N2 - 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.

AB - 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.

KW - antipsychotic agents

KW - atypical antipsychotic

KW - neuroleptic

KW - schizophrenia

KW - D(2)

KW - D(3)

KW - dopamine

KW - SPECT

KW - photon emission tomography

KW - [(123)I]epidepride

KW - EMISSION-TOMOGRAPHY SPET

KW - IN-VIVO

KW - ANTIPSYCHOTIC-DRUGS

KW - PARKINSONS-DISEASE

KW - TREATED PATIENTS

KW - BASAL GANGLIA

KW - ATYPICAL ANTIPSYCHOTICS

KW - LIMBIC SELECTIVITY

KW - DOPAMINE-RECEPTORS

KW - HUMAN-BRAIN

U2 - 10.1007/s00213-005-2161-2

DO - 10.1007/s00213-005-2161-2

M3 - Article

SN - 0033-3158

VL - 180

SP - 664

EP - 669

JO - Psychopharmacology

JF - Psychopharmacology

IS - 4

ER -