Dopaminergic activities in the human striatum: rostrocaudal gradients of uptake sites and of D1 and D2 but not of D3 receptor binding or dopamine
Section snippets
Materials
General laboratory reagents were supplied by Sigma and Merck and were of analytical grade. Radioligands were from Amersham in the case of [3H]7-OH-DPAT and DuPont NEN for [3H]mazindol, [3H]7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390) and [methoxy-3H]raclopride. Ascorbic acid, bovine serum albumin and HEPES were obtained from Sigma. Butaclamol, desipramine, DA, cis-flupenthixol, idazoxan, ketanserin, nomifensine and R(−)-N
Results
Binding to the DA uptake sites and the D1, D2 and D3 receptors is illustrated in representative autoradiographic images in Fig. 2, as mean values in the different areas and coronal levels in Table 2, and as graphs to illustrate rostrocaudal distributions in Fig. 3, Fig. 4, Fig. 5, Fig. 6. DA and HVA concentrations (pmol per mg protein, mean±S.D.) and HVA/DA ratio are displayed in the rostrocaudal dimension in Fig. 7.
Discussion
The present study provides a comprehensive mapping of the distribution of DA D1, D2 and D3 receptor binding, together with DA uptake site binding and the level of DA and its metabolites in the striatum at coronal levels between the anterior caudate and internal globus pallidus. This allows comparisons between parameters dorsoventrally, lateromedially and rostrocaudally at six coronal levels of the striatum. The distribution patterns described and receptor binding values are consistent with
Conclusion
This study describes dramatic differences in the distribution of components of dopaminergic transmission in the human striatum, which may have functional significance. Notably, the presynaptic markers of DA uptake site binding in the nucleus accumbens and rostral caudate, together with DA content in the rostral caudate, were low, while in these regions postsynaptically D2 receptors were expressed at relatively low density, highlighting the importance of the D3 receptor (which has higher
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