Monoamines in the human neostriatum: topographic distribution in normals and in Parkinson's disease and their role in akinesia, rigidity, chorea, and tremor.

Abstract The topographical distributions of dopamine, norepinephrine, and serotonin were mapped in the human neostriatum in 6 normal brains and in 2 brains from patients with Parkinson's disease. The neostriatum was divided into putamen and four sections of the caudate nucleus: inferior and superior heads and rostral and caudal tails. In normal man, the monoamine occurring in highest concentration is dopamine, which is fairly evenly distributed throughout the entire neostriatum (at a concentration around 3500 ng/g) except for the caudal tail. This region has a concentration of dopamine only 20% of that in the remainder of the neostriatum. Norepinephrine is virtually non-existent in the neostriatum except in the inferior head of the caudate nucleus where a concentration of 262 ng/g is found. Serotonin is evenly distributed throughout the entire neostriatum at a concentration around 800 ng/g. The difference in the distribution of these three monoamines implies a difference in function among the regions of the neostriatum. There is evidence in the literature to support the concept of somatotopic localization in the neostriatum. In Parkinson's disease there is a reduction of all three monoamines, with the greatest loss of dopamine in the putamen. All regions of the caudate also show a reduction of dopamine, although this is less severe than in the putamen. Norepinephrine in the inferior head of the caudate nucleus is significantly reduced. Serotonin is unevenly reduced throughout the entire neostriatum. The uneven reduction of dopamine and serotonin appears to preclude the possibility of a defect in the transport of precursor amino-acids into brain and in the synthesis, storage, and degradation of the monoamines in Parkinson's disease. Rather, it seems that the most likely explanation of these results is a defect of the neuronal cell bodies that contain monoamines and neuromelanin pigment. The etiology of such an unevenness of involvement of this system degeneration is not known, but could involve an infectious, nutritional, toxic, or other unknown factor. An analysis of the results in these patients and of the data in the literature also suggests that: (1) akinesia results from reduction of neostriatal dopamine; (2) rigidity is secondary to reduction of neostriatal dopamine plus some additional unknown factor; (3) chorea may be related to an increased dopamine/receptor ratio in the neostriatum and that serotonin and norepinephrine may also play a role; and (4) tremor at rest may result from reduced neostriatal content of dopamine and serotonin plus some additional factor, perhaps involvement of the rubro-olivo-cerebello-rubral loop or of rubrotegmentospinal fibers.