Agonist binding fraction of dopamine D23 receptors in rat brain a quantitative autoradiographic study.
There has arisen considerable interest in the study of dopamine D(23) agonist binding sites by positron emission tomography (PET), based on the claim that agonist sites represent a functional subset of the total number of sites labeled by more conventional antagonist ligands. To test the basis of this claim, we used quantitative autoradiography to measure the abundance of binding sites of a dopamine D(23) agonist ((3)HNPA) and an antagonist ((3)Hraclopride) in cryosections of rat brain. Saturation binding studies revealed that the B(max) for (3)HNPA was nearly identical to that of (3)Hraclopride in dorsal brain regions, but was 25% less in the ventral striatum and 56% less in the olfactory tubercle. We also tested the displacement of the two ligands by the hallucinogen LSD, which is known to have dopamine agonist properties. Whereas displacement of (3)Hraclopride by increasing LSD concentrations was monophasic, displacement of (3)HNPA was biphasic, suggesting an action of LSD via a subset of dopamine D(23) agonist binding sites. Addition of the stable GTP analogue Gpp(NH)p to the medium abolished 90% of the (3)HNPA binding, and increased (3)Hraclopride binding by 10%, with a shift to the right in the LSD competition curve, suggesting retention of endogenous dopamine in washed cryostat sections. Thus (3)HNPA and (3)Hraclopride binding sites have nearly identical abundances in rat dorsal striatum, but are distinct in the ventral striatum, and with respect to their displacement by LSD.