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Agonist binding fraction of dopamine D2/3 receptors in rat brain: a quantitative autoradiographic study.

Abstract：

:There has arisen considerable interest in the study of dopamine D(2/3) 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(2/3) agonist ([(3)H]NPA) and an antagonist ([(3)H]raclopride) in cryosections of rat brain. Saturation binding studies revealed that the B(max) for [(3)H]NPA was nearly identical to that of [(3)H]raclopride 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)H]raclopride by increasing LSD concentrations was monophasic, displacement of [(3)H]NPA was biphasic, suggesting an action of LSD via a subset of dopamine D(2/3) agonist binding sites. Addition of the stable GTP analogue Gpp(NH)p to the medium abolished 90% of the [(3)H]NPA binding, and increased [(3)H]raclopride 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)H]NPA and [(3)H]raclopride 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.

journal_name

Neurochem Int

journal_title

Neurochemistry international

authors

Minuzzi L,Cumming P

doi

10.1016/j.neuint.2010.01.010

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

747-52

issue

6-7

eissn

0197-0186

issn

1872-9754

pii

S0197-0186(10)00045-8

journal_volume

56

pub_type

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