Autoradiographic localisation of D-3-dopamine receptors in the human brain using the selective D-3-dopamine receptor agonist (+)-[H-3]PD 128907

The selective D-3-dopamine receptor agonist 4aR,10bR-(+)-trans-3,4,4a,10b-tetrahydro-4-[N-propyl-2,3- H-3]-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol ([H-3]PD 128907) was used to visualise D-3-dopamine receptors in whole hemisphere cryosections from post-mortem human brain. [H-3]PD 128907 has an 18- to 40-fold selectivity for D-3- over D-2-dopamine receptors as compared to a 7- to 24-fold selectivity of the more commonly used ligand [H-3]7-OH-DPAT. [H-3]PD 128907 accumulated markedly in the nucleus accumbens and in the ventral parts of caudate nucleus and putamen, with a slightly heterogeneous (patch-matrix like) distribution. The binding in the lateral parts of caudate nucleus and putamen was much less dense. No binding was obtained in any other regions. A very high proportion of [H-3]PD 128907 was specifically bound, as judged from the low binding remaining in the presence of the D-2/D-3-dopamine receptor antagonist raclopride. This gives the ligand a potential for the detection of low density D-3-dopamine receptors in the human brain. The binding obtained with [H-3]PD 128907 was clualitatively similar to that using [H-3]7-OH-DPAT in the presence of GTP. However, [H-3]7-OH-DPAT labelled, in contrast to [H-3]PD 128907, also D-3-dopamine receptors in neocortex, The new compound [H-3]PD 128907 appears to be a suitable radioligand for autoradiographic examination of the D-3-dopamine receptor localisation in the human brain, and should also be useful for pharmacological studies of this receptor subtype.