Distribution of catecholamine uptake sites in human brain as determined by quantitative [3H] mazindol autoradiography.
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.
Donnan
G A
GA
Department of Neurology, Austin Hospital, Melbourne, Australia.
Kaczmarczyk
S J
SJ
Paxinos
G
G
Chilco
P J
PJ
Kalnins
R M
RM
Woodhouse
D G
DG
Mendelsohn
F A
FA
D000368:Aged; D001590:Benztropine / Q000494:pharmacology; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D001923:Brain Chemistry; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D002997:Clomipramine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism; D008454:Mazindol / Q000493:pharmacokinetics; D008526:Medulla Oblongata / Q000378:metabolism; D008803:Mianserin / Q000494:pharmacology; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011149:Pons / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism
D010879:Piperazines; D015283:Citalopram; D001590:Benztropine; D008803:Mianserin; C043425:vanoxerine; D008454:Mazindol; D002997:Clomipramine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine