Journal
SCHIZOPHRENIA RESEARCH
Volume 131, Issue 1-3, Pages 63-68Publisher
ELSEVIER
DOI: 10.1016/j.schres.2011.05.005
Keywords
D3 receptors; [C-11]-(+)-PHNO; Antipsychotic; Positron Emission Tomography (PET); Schizophrenia
Categories
Funding
- Canadian Institutes for Health Research [157739, MOP 74702]
- Canada Foundation for Innovation
- Ontario Innovation Trust
- Ontario Research and Development Challenge Fund
- Canadian Institutes of Health Research (CIHR)
- Ontario Mental Health Foundation
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Most antipsychotics are thought to have an effect on D-2 and D-3 receptors, although their D-3, versus D-2 binding has not been clearly established in vivo in humans. However, the development of [C-11]-(+)-PHNO now permits the differentiation of antipsychotic activity on these two receptor subtypes. In this study we examined the effects of antipsychotics on D-2 and D-3 receptors by comparing [C-11]-(+)-PHNO in D-2-rich (caudate, CAU and putamen, PUT), mixed (ventral striatum) and D-3-rich (globus-pallidus, GP and substantia nigra, SN) regions before and after the initiation of antipsychotic medication. The investigation therefore represents a longitudinal within-subject follow-up design wherein antipsychotic-naive patients with schizophrenia spectrum disorders were first scanned in a drug-naive state and then again after similar to 2.5 weeks of antipsychotic treatment (risperidone or olanzapine). Binding potential (non displaceable or BPND) was obtained to derive estimates of drug occupancy in the identified brain regions. Antipsychotic treatment was associated with the expected occupancies in the D-2-rich regions: unexpectedly though, patients showed a higher, rather than the expected lower, [C-11]-(+)-PHNO BPND in the GP and SN despite simultaneous evidence for ongoing D-2 blockade in the other regions (CAU and PUT). In conclusion, patients treated with atypical antipsychotics demonstrated no evidence of D-3 receptor occupancy, but instead possible D-3 up-regulation following short-term treatment. The present findings add to a very limited body of evidence related to D-3 binding in vivo. [C-11]-(+)-PHNO offer new opportunities for exploring the potential therapeutic significance of the D-3 receptor in schizophrenia and the action of antipsychotics. (C) 2011 Elsevier B.V. All rights reserved,
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