In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist11C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate

Autor: Bradley T. Christian, Joseph Mantil, Kelly Dunigan, Tanjore K. Narayanan, Jogeshwar Mukherjee, Bingzhi Shi
Rok vydání: 2000
Předmět:
Zdroj: Synapse. 37:64-70
ISSN: 1098-2396
0887-4476
DOI: 10.1002/(sici)1098-2396(200007)37:1<64::aid-syn7>3.0.co;2-f
Popis: The in vitro autoradiographic binding characteristics as well as in vivo imaging characteristics of a dopamine D2 receptor agonist, (R,S)-2-(N-propyl-N-1′-11C-propyl)amino-5-hydroxytetralin (11C-5-OH-DPAT), were studied. In 3H-spiperone assays using rat striata, 5-OH-DPAT exhibited an affinity of IC50 = 2.5 nM. In vitro autoradiographs in rat brain slices with 11C-5-OH-DPAT revealed selective binding to the dopaminergic regions in the striata which was displaceable by sulpiride. Varying concentrations of dopamine displaced this selective binding of 11C-5-OH-DPAT to the striata in rat brain slices. This selective binding to the striata was also removed in the presence of the GTP analog, 5′-guanylylimidodiphosphate, indicative of the binding of 11C-5-OH-DPAT to the high-affinity state of the D2 receptor. Ex vivo autoradiographic study in rats exhibited selective binding of 11C-5-OH-DPAT to the striata. A PET study in a rhesus monkey showed selective localization of 11C-5-OH-DPAT in the striata and the ratio between striata and cerebellum approached approximately 2 at 40 min postinjection. Synapse 37:64–70, 2000. © 2000 Wiley-Liss, Inc.
Databáze: OpenAIRE
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