Correlative neuroanatomical and neuropharmacological study of tremor and catatonia in the monkey

Physiopathology of Experimental Parkinsonism in the Monkey

“…Therefore these results point to the importance of the inactivation of the neostriatal DA mechanisms in the production of postural tremor. This is further supported by the fact that reserpine which depletes monoamines stores, and thioproperazine, which, like other phenothiazine derivatives, blocks the dopamine receptors, also induce tremor in monkeys with lesions of the rubro-olivo-cerebellorubral loop (Larochelle et al, 1971). The Parkinson-like syndrome (including postural tremor) observed following the chronic administration of reserpine, and phenothiazine and butyrophenone derivatives (see references above) to non-Parkinsonian patients further substantiates the possibility that the involvement of brain monoaminergic mechanisms represents an important factor in the appearance of tremor and other signs of Parkinsonism.…”

“…for a period of approximately 45 min. Larochelle et al, 1971). This effect is most likely related to the conversion of dopa to dopamine within the terminals of the nigrostriatal pathways which are spared in animals with such lesions.…”

“…In view of the fact that the neostriatum (caudate nucleus and putamen) is rich in acetylcholine and the corresponding metabolic enzymes, cholinesterase and choline acetylase, it is conceivable that the cholinergic mechanisms of the neostriatum deprived of the influence of the dopaminergic endings (as a consequence of the interruption of the nigrostriatal pathway or the pharmacological inactivation of the DA mechanisms) play an important role in the production of the abnormal rhythmic bursts associated with postural tremor (Figure 2). In this respect it is worth mentioning that postural tremor induced in lesioned monkeys by AMT, reserpine and thioproperazine is abolished by benztropine (Larochelle et al, 1971). It is also pertinent to mention that the internal division of the pallidum which is involved in the production of tremor (cf postea) is recipient of important cholinesterasic (Olivier et al, 1970) and gabaminergic (Kim et al, 1971) nervous fascicles originating in the neostriatum.…”

“…The fact that L-DOPA may suppress reserpine-induced rigidity in these patients (Degkwitz et al, 1960) in whom the nigrostriatal DA mechanisms are presumably intact supports the idea that a brain catecholamine decrease or inactivation represents an important contributory factor in the genesis of rigidity. The administration of a single or a few large doses of reserpine or phenothiazine and butyrophenone derivatives most often do not result in rigidity (Bedard, 1971) despite the associated monoaminergic disturbances. The production of rigidity therefore appears to involve the long-term metabolic effects of these drugs which may interfere with various centers of the CNS in addition to their more specific effects on monoaminergic mechanisms.…”

“…Bradykinesia without rigidity and tremor have been produced in non-lesioned animals by the injection of single dose of the above-mentioned drugs. Moreover bradykinesia induced by reserpine may be transiently counteracted by L-DOPA (Larochelle et al, 1971). Akinesia whose severity is dosedependent may also be produced in non-lesioned monkeys by the administration of alpha-methyltyrosine (AMT), a tyrosine hydroxylase inhibitor (Spector et al, 1965).…”