Melatonin and Abnormal Movements Induced by L-Dopa in Mice

Cotzias, George C.; Tang, Lei-Han; Miller, Samuel T.; Ginos, James Z.

doi:10.1126/science.173.3995.450

Cited by 84 publications

(29 citation statements)

References 13 publications

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“…Nor was there any change in NA or dopamine in these areas (Table 2). Much larger doses of melatonin have been reported to increase brain dopamine content in mice (Cotzias, Tang, Miller & Ginos, 1971). The lack of a significant change in indoleamines and catecholamines found in the study described here does not preclude the possibility that the sleep promoting action of melatonin may involve more subtle changes in these neurotransmitter systems.…”

Section: Discussionmentioning

confidence: 40%

Effects of Melatonin on Sleep and Neurochemistry in the Rat

Holmes

Sugden

1982

British J Pharmacology

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The effects of intraperitoneally administered melatonin on sleep and brain neurochemistry in the rat were studied by use of EEG recording and standard fluorescence techniques. Melatonin, 10 mg/kg, reduced time to sleep onset and time spent awake but increased both slow wave and paradoxical sleep. Qualitatively similar but smaller effects were produced by a dose of 2.5 mg/kg. Neither dose of melatonin altered normal EEG patterns or disrupted normal sleep behaviour. Melatonin, 20 mg/kg, did not significantly alter concentrations of tryptophan, 5‐hydroxytryptamine, 5‐hydroxyindoleacetic acid, noradrenaline or dopamine in any part of the brain. It is concluded that the sleep promoting activity of melatonin cannot be related to gross changes in brain indoleamine and catecholamine levels.

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Section: Discussionmentioning

confidence: 40%

Effects of Melatonin on Sleep and Neurochemistry in the Rat

Holmes

Sugden

1982

British J Pharmacology

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“…When intact animals were given nialamide (0.5, 0.25, 0.125, and 0.1 mg/g, i.p.) followed by dopamine, their placidity lasted maximally for 10 min and was followed by dose-dependent motor hyperactivity and the other effects characteristic of L-dopa (17) were inactive, these experiments suggested that the MAO inhibitors had permitted extensive entrance of exogenous dopamine into brain areas, including the striatum.…”

Section: Observationsmentioning

confidence: 86%

“…Whole brain dopamine was determined fluorimetrically (16) in intact mice 30 min after the injection of either water or dopamine (17). Cerebral radioactivity was measured periodically on pairs of water-or nialamide-pretreated mice after injection of tritiated apomorphine (18).…”

mentioning

confidence: 99%

Monoamine Oxidase and Cerebral Uptake of Dopaminergic Drugs

Cotzias¹,

Tang²,

Ginos³

1974

Proc. Natl. Acad. Sci. U.S.A.

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The brain uptake of amines that do not enter the brain or enter it poorly was promoted by noncompetitive inhibitors of monoamine oxidase, as shown by behavioral and chemical criteria. Mice pretreated with water or enzyme inhibitors other than those mentioned were placid after receiving dopamine (3,4-dihydroxyphenethylamine). Mice pretreated with monoamine oxidase inhibitors (nialamide or iproniazid) showed upon treatment with dopamine the brisk motor responses characteristic of treatment with its precursor, L-dopa (3,4-dihydroxyphenylalanine). After receiving dopamine, intact nialamide-pretreated mice showed marked increases of brain dopamine, in contrast to water-pretreated test mice or water-treated controls. In unilaterally caudectomized, nialamide-pretreated mice, dopamine induced marked lateral curving of the body toward the lesion followed by running in that direction. Noradrenaline or adrenaline induced curving in caudectomized mice, whereas intact ones remained placid.These catecholamines are bound and inactivated by monoamine oxidase. The cerebral uptakes of chemicals that are bound but not inactivated by monoamine oxidase were thereafter tested. Nialamide induced increased behavioral responses to apomorphine and to N-propyl noraporphine, increased cerebral concentrations of both, and a deep coloration of the brain from methylene blue (bound by monoamine oxidase) but not Evans blue (bound by albumin). Even large doses of nialamide, however, failed to affect the behavioral responses to oxotremorine, which has cholinergic rather than adrenergic or dopaminergic properties. Mitochondrial monoamine oxidase seems therefore to play a specific regulatory role in the transport of substances that it binds, either to inactivate or to release them.

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“…Melatonin, in turn has been shown to affect dopamine-mediated behaviors and neuroendocrine functions in experimental animals (Kovacs et al, 1974;Blask et al, 1980;Golus & King, 1981;Bradbury et al, 1985;Gaffori & Van Ree, 1985) and to inhibit L-dopa-induced dyskinesia in mice (Cotzias et al, 1971). Conversely, in rats, pinealectomy reportedly enhances the emergence of neuroleptic-induced purposeless chewing movements, a motor behavior which is related to increased striatal dopaminergic activity and which is considered an animal model for Tardive dyskinesia (Sandyk & Fisher, 1989).…”

Section: Proposed Mode Of Action Of Magnetic Fieldsmentioning

confidence: 99%