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Dopamine D 2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine
Author(s) -
Tuppurainen Heli,
Kuikka Jyrki T.,
Viinamäki Heimo,
Husso Minna,
Tiihonen Jari
Publication year - 2009
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/j.1440-1819.2009.01982.x
Subject(s) - clozapine , olanzapine , dopamine , haloperidol , dopamine antagonist , schizophrenia (object oriented programming) , psychosis , dopamine receptor d2 , psychology , medicine , antipsychotic , pharmacology , endocrinology , neuroscience , psychiatry
Aims: Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second‐generation antipsychotics in dopamine D 2 receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D 2/3 receptor apparent binding potential (BP app ) and occupancy in midbrain and temporal cortex among clozapine‐, olanzapine‐ and haloperidol‐treated schizophrenia patients. Methods: Dopamine D 2/3 binding was studied on single‐photon emission computed tomography ligand [ 123 I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug‐naïve patients and seven healthy controls. Results: Statistically significant differences in midbrain dopamine D 2/3 receptor BP app ( P = 0.015) and occupancy ( P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine‐treated patients (5%), followed by olanzapine‐treated patients (28%), compared to haloperidol‐treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug‐naïve vs healthy controls) in the examined brain areas ( P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used. Conclusion: Both typical and second‐generation antipsychotics occupy cortical dopamine D 2/3 receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D 2/3 occupancy between classical antipsychotics and second‐generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.