Dopamine D2 receptors mapped in rat brain with [3H](+)PHNO.
Previous work with membrane preparations had demonstrated that the agonist (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) labels the high-affinity state of dopamine D2 receptors with 67-fold selectivity over D1 sites. In this study, quantitative autoradiography was used to examine the binding of [3H](+)PHNO to rat brain sections. Highest binding densities were found in caudate-putamen, accumbens, and olfactory tubercles, as expected, and also in specific layers of the olfactory bulb. In addition, a second group of brain regions, including lateral septum, entorhinal cortex, molecular layer of hippocampus, and several brainstem structures showed low but consistent levels of binding. In all brain regions [3H](+)PHNO binding (2 nM) was completely displaced by 10 microM sulpiride (> 99%). Addition of 150 microM guanilylimidodiphosphate, which normally converts D2 receptors from high to low affinity states, abolished [3H](+)PHNO binding in all brain regions (> 99%), except for the islands of Callejas. This is likely to reflect binding to D3 sites in this area. Omission of preincubation in binding assays decreased [3H](+)PHNO binding in a regionally dependent manner, with strongest effects (22%) seen in high-density areas. These preincubation results confirm that (+)PHNO may have limitations for in vivo imaging studies. On the other hand, [3H](+)PHNO's negligible levels of non-specific binding compared to other agonists and overall selectivity would make it an excellent tool for in vitro autoradiographic monitoring of the high affinity state of D2 receptors.
Nobrega
J N
JN
Neuroimaging Research Section, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Seeman
P
P
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D001931:Brain Mapping; D003720:Densitometry; D018491:Dopamine Agonists; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006150:Guanine Nucleotides / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010078:Oxazines; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D012457:Salicylamides / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D006150:Guanine Nucleotides; D008024:Ligands; D010078:Oxazines; D012457:Salicylamides; C042631:naxagolide; D006165:Guanylyl Imidodiphosphate; D020891:Raclopride; D013134:Spiperone