Premium
In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist 11 C‐( R,S )‐5‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin in rodents and nonhuman primate
Author(s) -
Mukherjee Jogeshwar,
Narayanan Tanjore K.,
Christian Bradley T.,
Shi Bingzhi,
Dunigan Kelly A.,
Mantil Joseph
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(200007)37:1<64::aid-syn7>3.0.co;2-f
Subject(s) - spiperone , agonist , in vivo , dopamine , dopaminergic , gtp' , chemistry , binding site , dopamine receptor d2 , receptor , dopamine receptor , in vitro , biology , medicine , stereochemistry , endocrinology , microbiology and biotechnology , biochemistry , enzyme
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′‐ 11 C‐propyl)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 = 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, 5′‐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. Synapse 37:64–70, 2000. © 2000 Wiley‐Liss, Inc.