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Girgis, Ragy R; Xu, Xiaoyan; Gil, Roberto B; Hackett, Elizabeth; Ojeil, Najate; Lieberman, Jeffrey A; Slifstein, Mark; Abi-Dargham, Anissa
Schizophrenia research, 10/2015, Letnik: 168, Številka: 1Journal Article
Abstract Background All currently available antipsychotic medications bind to both the dopamine-2 (D2) and dopamine-3 (D3) receptors in vitro . However, there is conflicting evidence from in vivo studies about whether or not antipsychotic medications bind to the D3 receptor (D3R). The purpose of this study was to determine whether acute doses of risperidone bind to the D3R in humans. Methods We performed PET scans on an mCT scanner with 11 C-(+)-PHNO injected as a bolus, before and after a 2 mg oral dose of risperidone in five medication free subjects with schizophrenia. The subjects were scanned for 120 min and underwent an MRI scan for region of interest delineation and coregistration. Cerebellum was used as a reference region. Simplified reference tissue modeling (SRTM) was used to calculate BPND. Results We observed binding to the D3R receptor by risperidone as evidenced by observable occupancy in regions in which the 11 C-(+)-PHNO signal is almost exclusively from the D3R ( i.e. , substantia nigra/ventral tegmental area). Using a regression model to estimate D2R:D3R selectivity, we observed a D2R:D3R selectivity of 2.1 for risperidone. Conclusion Our preliminary results provide further support that acute doses of antipsychotic medications bind to the D3R and provide additional support for the further development of this receptor as a treatment target in schizophrenia.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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