In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist 11C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate

✍ Scribed by Jogeshwar Mukherjee; Tanjore K. Narayanan; Bradley T. Christian; Bingzhi Shi; Kelly A. Dunigan; Joseph Mantil

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 158 KB
• Volume: 37
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(200007)37:1<64::aid-syn7>3.0.co;2-f

✦ Synopsis

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-1Ј-11 Cpropyl)amino-5-hydroxytetralin ( 11 C-5-OH-DPAT), were studied. In 3 H-spiperone assays using rat striata, 5-OH-DPAT exhibited an affinity of IC 50 ϭ 2.5 nM. In vitro autoradiographs in rat brain slices with 11 C-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 11 C-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, 5Ј-guanylylimidodiphosphate, indicative of the binding of 11 C-5-OH-DPAT to the high-affinity state of the D2 receptor. Ex vivo autoradiographic study in rats exhibited selective binding of 11 C-5-OH-DPAT to the striata. A PET study in a rhesus monkey showed selective localization of 11 C-5-OH-DPAT in the striata and the ratio between striata and cerebellum approached approximately 2 at 40 min postinjection.