Neurochemical bases of tremor and other disorders of movement.

Monkeys inflicted with specific unilateral electrolytic lesions in the upper brain stem developed extrapyramidal disorders. Hypokinesia of the limbs was associated contralaterally with a lesion of the substantia nigra and depletion of striatal dopamine. Choreiform movements were observed in animals that had, contralaterally, a lesion severing the most dorsomedial fibres of the cerebral peduncle and the rubro-tegmentospinal tract, associated with depletion of striatal serotonin. Monkeys showing sustained postural tremor and hypokinesia had lesions affecting these three tracts contralaterally and loss of striatal dopamine and serotonin on the lesion side. Of many drugs tested, only harmaline and harmine affected the dyskinesias. The nigrostriatal fibres appear to be dopaminergic; the cerebral peduncular (dorsomedial) fibres, serotoninergic. The role of striatal dopamine and serotonin in the control of normal movements and posture of the limbs represents the first directly demonstrated function of these amines in the central nervous system.