Dopaminergic activities in the human striatum: rostrocaudal gradients of uptake sites and of D1 and D2 but not of D3 receptor binding or dopamine.

The human striatum, which receives dopaminergic innervation from the substantia nigra and ventral tegmental area (cell groups A8, A9 and A10), has structural and functional subdivisions both rostrocaudally and dorsoventrally. These relate to motor and non-motor origins of cortical projections and the specific areas of the substantia nigra and ventral tegmental area providing dopaminergic innervation. In the present study, we have evaluated the distribution of a number of dopaminergic parameters in the caudate, putamen and nucleus accumbens at separate coronal levels in a post mortem study in a series of elderly normal individuals aged 55-94 years, with analysis of the effect of post mortem variables. Dopamine D1 receptor density displayed a rostrocaudally declining gradient in the putamen but not in the caudate, such that at levels posterior to the anterior commissure, there was significantly lower D1 binding in the putamen compared to the caudate. The density of dopamine D2 receptors was similar in the putamen and caudate, increasing rostrocaudally. The density of dopamine uptake sites exhibited an increasing rostrocaudal gradient in the caudate, especially ventrally, but not in the putamen, where binding was more constant. The dopamine D3 receptor was concentrated in the ventral striatum, particularly the nucleus accumbens, although there was no evidence of a rostrocaudal gradient. With respect to striosome-matrix compartmentalization, there was no complete segregation, although D1 and D3 receptors were concentrated in striosomes, whereas D2 receptors and uptake sites showed higher density in the matrix. Levels of dopamine were similar in the caudate and putamen, and were significantly elevated at levels including the nucleus accumbens and the anterior commissure. Homovanillic acid and the metabolic index (homovanillic acid/dopamine ratio) were significantly higher in the putamen compared to the caudate, especially at levels from and caudal to the anterior commissure. These distributions of dopamine receptors and 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 disorders. They provide information to assist in the detection of perturbations in expression, in specific diseases, at particular points on rostrocaudal, lateromedial and dorsoventral axes, a level of resolution beyond current neuroimaging capability.