The Effects of Centrally Acting Drugs on Tremor in Monkeys With Mesencephalic Lesions

Abstract

Abstract.-The effects of centrally acting drugs on tremor were investigated in monkeys with ventromedial tegmental lesions exhibiting hypokinesia or hypokinesia and tremor. In monkeys with resting tremor, the administration of DL-5-HTP (5-hydroxytryptophan) or of DL-DOPA (3,4-dihydroxyphenylalanine) relieves the tremor, but the simultaneous administration of DL-5-HTP or DL-DOPA and atropine results in a much more pronounced relief. These results point to an imbalance between the cholinergic and adrenergic-serotonergic systems in parkinsonism.In monkeys exhibiting hypokinesia, the administration of harmaline evokes a marked resting tremor of the extremities contralateral to the tegmental lesion. The production of tremor by harmaline is not abolished by lowering the striatal amine levels with specific inhibitors of amine synthesis. Administration of DL-5-HTP protects monkeys from tremors induced by harmaline, which might affect the functions of the central nervous system by interaction with receptors for serotonin. The present results further demonstrate the apparent role of biogenic amines in the extrapyramidal dysfunctions.Model syndromes of extrapyramidal dysfunction have been produced in monkeys by introduction of unilateral lesions into the ventromedial area of the brain stem, after which the destruction of the pars compacta of the substantia nigra is associated with low concentrations of dopamine and serotonin in the corresponding basal ganglia.' Reduction of the biogenic amines in the striatum is concomitant with an impairment in the storage of dopamine and serotonin and with a decrease in the activities of tyrosine hydroxylase and DOPA decarboxylase.2-4To determine further the role of biogenic amines in extrapyramidal dysfunction, we have investigated the effects of centrally acting drugs on tremor in monkeys with mesencephalic lesions.Methods. -Green monkeys (Cercopithecus sabaeus) were used and unilateral radio-frequency lesions were induced in the ventromedial tegmental region of the brain stem as previously described.1' 2 Hypokinesia of the contralateral extremities appeared immediately afterward. In some monkeys a resting tremor (4 to 6 cycles per sec) developed five to seven days later. The lesions were induced at least one month prior to the beginning of the experiments. Tremograms were obtained by means of a transducer attached to the extremities and recorded on an electroencephalograph. The effects of centrally acting drugs were investigated in monkeys with ventromedial tegmental lesions with a slight spontaneous resting tremor of the contralateral extremities (group I) and in monkeys exhibiting hypokinesia of the contralateral extremities but no resting tremor (group II). Localization of the lesion in each brain was verified by gross examination and by histological studv. The locus and the extent of the lesion were similar to those reported previously.' Gross examination revealed that the lesion in the monkeys from group I was 1113

Release of 5‐hydroxytryptamine from caudate nucleus and septum

“…One functional significance of the tryptaminergic pathway to the caudate is suggested by the fact that its destruction appears to play a role in Parkinsonian tremor. At least in the monkey exhibiting tremor as a result of a tegmental lesion, the administration of 5-hydroxytryptophan arrests the tremor (Goldstein, Battista, Nakatani & Anagnoste, 1969).…”

Animal models of tremor

“…In primates, unilateral lesions of the ventromedial tegmentum produce tremor in the contralateral extremities. [180][181][182][183] This tremor is present at rest and under postural innervation (4-8 cycles/sec), it develops several days postoperatively, and is more pronounced in the upper extremity. Occasionally pill-rolling tremor is observed.…”

Facilitatory and Inhibitory Effects of Harmaline on the Tryptophan-Induced 5-Hydroxytryptamine Syndrome and Body Temperature Changes in Pargyline-Pretreated Rats

“…In spite of a number of studies on harmaline and other harmala alkaloids, the actions of harmaline on the central 5-HT systems in vivo are still controversial. For example, the harmaline-induced tremor is inhibited by 5-HTP in monkeys (24,25), while coadministration of harmaline with 5-HTP reportedly causes a lethal convulsive myoclonic syndrome (26). Thus, in this study, to further clarify the mechanisms underlying the action of harmaline on the central 5-HT systems activated by endogenous 5-HT, we investigated the effects of harmaline on the 5-HT syndrome and body temperature changes caused by tryptophan in pargyline-pretreated rats.…”