The International Journal of Neuropsychopharmacology

Research Article

No regional difference in dopamine D2 receptor occupancy by the second-generation antipsychotic drug risperidone in humans: a positron emission tomography study

Hiroshi Itoa1 c1, Ryosuke Arakawaa1, Hidehiko Takahashia1, Harumasa Takanoa1, Masaki Okumuraa1, Tatsui Otsukaa1, Yoko Ikomaa2, Miho Shidaharaa2 and Tetsuya Suharaa1

a1 Clinical Neuroimaging Team, Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan

a2 Image Analysis Team, Biophysics Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan

Abstract

The effects of antipsychotic drugs have generally been considered to be mediated by blockade of dopamine D2 receptors. The concept of limbic and cortical selectivity of second-generation antipsychotics, i.e. higher dopamine D2 receptor occupancy in the cerebral cortices than in the striatum, has been suggested to explain their clinical efficacy with lower incidence of extrapyramidal side-effects. In this study, regional distribution of dopamine D2 receptor occupancy by risperidone was determined in order to elucidate the limbic and cortical selectivity of second-generation antipsychotics. Striatal and extrastriatal dopamine D2 receptor binding at baseline and after oral administration of 2 mg risperidone were measured in ten healthy men by positron emission tomography (PET) using different tracers with different affinity for the receptors, [11C]raclopride and [11C]FLB 457, respectively. Striatal and extrastriatal occupancies of dopamine D2 receptors were calculated for each brain region. Occupancies of dopamine D2 receptors were about 70% and 60% in the striatum and extrastriatum, respectively. A simulation study showed that non-negligible specific binding in the reference region (cerebellum), could cause systemic underestimation of occupancy in [11C]FLB 457 PET studies, indicating that occupancies in both the striatum and extrastriatum may not have differed. Among the extrastriatal regions including limbic and neocortical regions, no significant regional differences in dopamine D2 receptor occupancy were observed. Thus, limbic and cortical selectivity was not observed by one of the second-generation antipsychotics, risperidone.

(Received April 24 2008)

(Reviewed June 13 2008)

(Revised September 02 2008)

(Accepted September 10 2008)

(Online publication October 23 2008)

Correspondence:

c1 Address for correspondence: H. Ito, M.D., Ph.D., Clinical Neuroimaging Team, Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Tel.: (+81) 43-206-4702 Fax: (+81) 43-253-0396 E-mail: hito@nirs.go.jp