AUTORADIOGRAPHIC LOCALIZATION 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 R-(+)-trans-3,4,4a,10b-tet rahydro-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 w hole hemisphere cryosections from post-mortem human brain. [H-3]PD 128 907 has an 18- to 40-fold selectivity for D-3- over D-2-dopamine recep tors as compared to a 7- to 24-fold selectivity of the more commonly u sed 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 puta men, with a slightly heterogeneous (patch-matrix like) distribution. T he binding in the lateral parts of caudate nucleus and putamen was muc h less dense. No binding was obtained in any other regions. A very hig h 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 rece ptor antagonist raclopride. This gives the ligand a potential for the detection of low density D-3-dopamine receptors in the human brain. Th e binding obtained with [H-3]PD 128907 was clualitatively similar to t hat using [H-3]7-OH-DPAT in the presence of GTP. However, [H-3]7-OH-DP AT labelled, in contrast to [H-3]PD 128907, also D-3-dopamine receptor s in neocortex, The new compound [H-3]PD 128907 appears to be a suitab le radioligand for autoradiographic examination of the D-3-dopamine re ceptor localisation in the human brain, and should also be useful for pharmacological studies of this receptor subtype.