[The life history of brain dopamine]

Neurochemical studies in Parkinson's disease have greatly contributed to the understanding of the neurobiology of the meso-telencephalic dopamine (DA) system; in addition, these studies have significantly influenced our concepts regarding the general principles of brain function. The primary role of DA in striatal function can be seen in its ability to initiate complex patterns of motor activity. The nigro-striatal DA system shows in the face of partial damage an extraordinarily high degree of plasticity, i.e. capacity for functional compensation. The two most important mechanisms of plasticity of the nigro-striatal DA system are: compensatory activation of the presynaptic remaining DA neurons (through increase in DA turnover); and increase in the number of postsynaptic DA receptors. The DA loss which occurs during normal ageing is not of sufficient magnitude to cause clinically overt Parkinson's disease. On the other hand, the observations pertaining to the Parkinsonian syndrome produced by NMPTP suggest the participation of environmental factors in the aetiology of idiopathic Parkinson's disease. The remarkable results of nigral cell transplants into the striatum of animals with experimental "parkinsonism", as well as the high therapeutic efficacy of DA substitution in patients with Parkinson's disease point toward a neurohumoral, rather than neurotransmitter, function of brain DA.