Dopaminergic activities in the human striatum: Rostrocaudal gradients of uptake sites and of D-1 and D-2 but not of D-3 receptor binding or dopamine

The human striatum, which receives dopaminergic innervation from the substa ntia nigra and ventral tegmental area (cell groups A8, A9 and A10), has str uctural and functional subdivisions both rostrocaudally and dorsoventrally. These relate to motor and non-motor origins of cortical projections and th e specific areas of the substantia nigra and ventral tegmental area providi ng dopaminergic innervation. In the present study, we have evaluated the distribution of a number of dop aminergic parameters in the caudate, putamen and nucleus accumbens at separ ate coronal levels in a post mortem study in a series of elderly normal ind ividuals aged 55-94 years, with analysis of the effect of post mortem varia bles. Dopamine D-1 receptor density displayed a rostrocaudally declining gr adient in the putamen but not in the caudate, such that at levels posterior to the anterior commisure, there was significantly lower D-1 binding in th e putamen compared to the caudate. The density of dopamine D-2 receptors wa s similar in the putamen and caudate, increasing rostrocaudally. The densit y of dopamine uptake sites exhibited an increasing rostrocaudal gradient in the caudate, especially ventrally, but not in the putamen, where binding w as more constant. The dopamine D-3 receptor was concentrated in the ventral striatum, particularly the nucleus accumbens, although there was no eviden ce of a rostrocaudal gradient. With respect to striosome-matrix compartment alization, there was no complete segregation, although D-1 and D-3 receptor s were concentrated in striosomes, whereas D-2 receptors and uptake sites s howed higher density in the matrix. Levels of dopamine were similar in the caudate and putamen, and were significantly elevated at levels including th e nucleus accumbens and the anterior commissure. Homovanillic acid and the metabolic index (homovanillic acid/dopamine ratio) were significantly highe r in the putamen compared to the caudate, especially at levels from and cau dal to the anterior commissure. These distributions of dopamine receptors a nd metabolic indicators, reflecting the different functional domains of the striatum, are relevant to the interpretation of current in vivo imaging of the dopamine transporter and receptors in neurological and psychiatric dis orders. They provide information to assist in the detection of perturbation s in expression, in specific diseases, at particular points on rostrocaudal , lateromedial and dorsoventral axes, a lever of resolution beyond current neuroimaging capability. (C) 1999 IBRO. Published by Elsevier Science Ltd.