The concept of a "dopamine motor system" has evolved as the result of a series of key basic science and clinical observations during the past 3 decades. Dopamine was first identified in forebrain homogenates using fluorescence analytic techniques nearly 30 years ago (1). With the development of the Falck-Hillarp histofluorescence technique, dopamine was identified in nerve terminals of the corpus striatum (2). Carlsson and colleagues observed that reserpine treatment led to a depletion of striatal dopamine and the appearance of a Parkinson-like syndrome in experimental animals (3). This reserpine-induced, Parkinson-like syndrome could be reversed by the administration of the dopamine precursor levodopa (3). Hornykiewicz was then able to make the observation that postmortem brain material from parkinsonian patients had markedly depleted dopamine levels in the striatum (4). Subsequently, Cotzias et al. showed that levodopa administration to patients with Parkinson's disease could ameliorate the clinical syndrome (5). Other evidence supporting the existence of a dopamine motor system in the brain included observations that neuroleptic drugs that are dopamine antagonists produced reversible parkinsonism in humans and laboratory animals, that explants of fetal nigral dopamine neurons or adrenal medullary cells capable of synthesizing and releasing dopamine could reverse parkinsonism (6), and that direct-acting dopamine agonists (e.g., apomorphine, bromocriptine) could do likewise.
Perhaps the most unequivocal evidence to date supporting a dopamine motor system are the observations of the potent neurotoxic effects of the opiate-like compound l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) on certain species. MPTP administration to primates results in histologically and neurochemically specific lesions of nigral dopamine neurons that result in striatal dopamine depletion and the emergence of parkinsonism. These observations taken together strongly suggest that striatal dopamine depletion is a sufficient condition for the emergence of the clinical syndrome of parkinsonism.
PHYSIOLOGICAL PROPERTIES OF DOPAMINE NEURONS
DeLong and Georgopoulos have made physiological recordings of neurons in the substantia nigra pars compacta (presumably dopamine neurons