Distribution of catecholamine uptake sites in human brain as determined by quantitative [³H] mazindol autoradiography

Abstract

Because of the importance of the catecholamine system in Parkinson's disease and its relevance to a variety of clinical movement disorders, catecholamine uptake sites were mapped in the human brain using [3H] mazindol autoradiography. Displacement studies with known dopamine (DA) and noradrenaline (NA) uptake blockers showed that binding in the striatum was to dopamine uptake sites; binding in the locus coeruleus was to noradrenergic uptake sites. By using the selective noradrenergic uptake blocker desmethylimipramine (DMI), a comprehensive map of both DA and NA uptake sites was generated. In general, catecholamine uptake sites were better seen in terminals than in cells of origin or axonal projections. In some areas, such as the locus coeruleus, punctate binding could be seen over individual pigmented cells. A variegated pattern of binding was seen in caudate nucleus and putamen and some correspondence of patches of low binding with striosomes was observed in the caudate. The highest levels of binding to DA uptake sites was observed in the striatum, where regional differences in binding occurred. The most dense binding was seen in the ventral striatum, and a rostral-to-caudal decrement in binding levels in caudate nucleus and putamen was evident. Binding was more intense in the putamen compared to the caudate and within the caudate lower values were seen laterally. The highest levels of binding to noradrenergic uptake sites were in the locus coeruleus and dorsal raphé, although these sites may be on terminals from other projections. Whereas uptake sites were more often evident in known catecholamine pathways, [3H] mazindol binding was seen in some areas where catecholamine neurons or terminals had not been identified previously. These maps of the catecholamine uptake system add further information concerning the nature of the distribution of catecholamines in human brain and provide an important baseline for the study of disease and ageing processes.

Pharmacology and Distribution of Norepinephrine Transporters in the Human Locus Coeruleus and Raphe Nuclei

“…Autoradiography of the binding of the highly selective NET radioligand [ 3 H]nisoxetine has revealed NET binding in the immediate region of the locus coeruleus, concentrations of which are the highest in the rat brain (Tejani-Butt et al, 1990;Tejani-Butt, 1992). Interestingly, moderate concentrations of [ 3 H]nisoxetine binding in a serotonergic cell body region, the dorsal raphe nucleus, have also been reported in rats (Tejani-Butt, 1992) and humans (Donnan et al, 1991). NET transporters in the dorsal raphe presumably reside on terminals of noradrenergic fibers that are known to innervate the dorsal raphe (Saavedra et al, 1976;Fuxe et al, 1978;Levitt and Moore, 1979;Baraban and Aghajanian, 1981) and illustrate the interconnection of the central noradrenergic and serotonergic neuronal systems.…”

“…[ 3 H]mazindol binds with high affinity to NETs but also binds to dopamine transporters so that nonspecific binding must be measured by careful choice of a displacing ligand and its concentration (Donnan et al, 1991). In contrast to these radioligands, [ 3 H]nisoxetine does not possess such complications.…”

Quantitative Analysis of Norepinephrine Transporter in the Human Brain Using PET with (S,S)-18F-FMeNER-D2

“…In these methods, (S,S)-18 F-FMeNER-D 2 bindings were expressed as binding potentials relative to nondisplaceable binding (BP ND ) (13). We used the caudate as the reference brain region because of its negligible norepinephrine transporter density (14)(15)(16). Software (PMOD; PMOD Technologies) was used for these analyses.…”

Compartmentalization of excitatory amino acid receptors in human striatum.

“…Striatal projection neurons contain y-aminobutyric acid as a neurotransmitter but may be differentiated by the presence or absence of neuropeptides such as substance P, dynorphin, and enkephalin (33,36,37 (42) or predominantly in striosomes (19,43), and in human, cholinergic Ml binding sites (25) have been reported to be increased in striosomes relative to matrix. D2 binding sites in rat (15), dopamine uptake sites in rat, cat, primate, and human (14,23,26), cholinergic uptake sites in human (25), and benzodiazepine receptors in human (44) are increased in matrix. The major inputs to the mammalian neostriatum are glutamatergic (or aspartergic) corticostriatal afferents (11,45).…”

“…Recent evidence suggests that the neostriatum is able to maintain segregated information flow due to compartmentalization in mammalian caudate and putamen (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Distinct regions within caudate and putamen have been defined in several species with histochemical techniques, in situ hybridization, and neurotransmitter receptor binding studies in rat (1,(12)(13)(14)(15), cat (10,14,(16)(17)(18)(19)(20), primate (12,14,(19)(20)(21)(22), and human (20,(23)(24)(25)(26). These compartments, termed striosomes and matrix, exhibit distinct afferent and efferent connections.…”