Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys

Porrino, L J; Burns, R S; Crane, A M; Palombo, E; Kopin, I J; Sokoloff, L

doi:10.1073/pnas.84.16.5995

Title: Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys

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Abstract

The quantitative 2-deoxy(/sup 14/C) glucose autoradiographic method was used to map the distribution of alterations in local cerebral glucose utilization that accompanies clinically effective chronic L-dopa therapy of rhesus monkeys made parkinsonian by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This pattern of changes was compared to the effects of a similar treatment regimen in normal monkeys. L-Dopa was administered orally to normal and parkinsonian monkeys 3 times daily for 60-120 days prior to measurement of local cerebral glucose utilization. In parkinsonian monkeys treated with L-dopa, signs and symptoms of parkinsonism were controlled or suppressed, and widespread increases in glucose utilization were seen throughout the brain. Cerebral metabolic activity was increased both in areas rich in dopaminergic receptors, such as the caudate and putamen, and in nondopaminergic areas involved in motor functions. In many structures the rates of glucose utilization in L-dopa-treated parkinsonian monkeys were increased to levels that far exceeded rates measured in normal monkeys. In sharp contrast, similar treatment with L-dopa in normal monkeys had little if any effect on local cerebral glucose utilization. L-Dopa, then, appears to have an action in animals with selective lesions of the substantia nigra pars compacta produced by MPTP that is distinctly different frommore » its effects in the normal monkey.« less

Authors:: Porrino, L J; Burns, R S; Crane, A M; Palombo, E; Kopin, I J; Sokoloff, L

Publication Date:: Sat Aug 01 00:00:00 EDT 1987

Research Org.:: National Institutes of Health, Bethesda, MD (USA)

OSTI Identifier:: 5295769

Resource Type:: Journal Article

Journal Name:: Proc. Natl. Acad. Sci. U.S.A.; (United States)

Additional Journal Information:: Journal Volume: 84:16

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; CARBON 14 COMPOUNDS; METABOLISM; CEREBRUM; AUTORADIOGRAPHY; DOPA; BIOLOGICAL EFFECTS; BEHAVIOR; GLUCOSE; MONKEYS; NERVOUS SYSTEM DISEASES; PHYSIOLOGY; ALDEHYDES; AMINO ACIDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; BRAIN; CARBOHYDRATES; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; DISEASES; DRUGS; HEXOSES; HYDROXY ACIDS; LABELLED COMPOUNDS; MAMMALS; MONOSACCHARIDES; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PRIMATES; SACCHARIDES; VERTEBRATES; 550501* - Metabolism- Tracer Techniques; 550201 - Biochemistry- Tracer Techniques

Citation Formats


                    Porrino, L J, Burns, R S, Crane, A M, Palombo, E, Kopin, I J, and Sokoloff, L. Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys.  United States: N. p., 1987. 
        Web.  doi:10.1073/pnas.84.16.5995.

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                    Porrino, L J, Burns, R S, Crane, A M, Palombo, E, Kopin, I J, & Sokoloff, L. Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys.  United States.  https://doi.org/10.1073/pnas.84.16.5995

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                    Porrino, L J, Burns, R S, Crane, A M, Palombo, E, Kopin, I J, and Sokoloff, L. 1987.  
        "Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys".  United States.  https://doi.org/10.1073/pnas.84.16.5995.

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@article{osti_5295769,

  title        = {Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys},

  author       = {Porrino, L J and Burns, R S and Crane, A M and Palombo, E and Kopin, I J and Sokoloff, L},

  abstractNote = {The quantitative 2-deoxy(/sup 14/C) glucose autoradiographic method was used to map the distribution of alterations in local cerebral glucose utilization that accompanies clinically effective chronic L-dopa therapy of rhesus monkeys made parkinsonian by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This pattern of changes was compared to the effects of a similar treatment regimen in normal monkeys. L-Dopa was administered orally to normal and parkinsonian monkeys 3 times daily for 60-120 days prior to measurement of local cerebral glucose utilization. In parkinsonian monkeys treated with L-dopa, signs and symptoms of parkinsonism were controlled or suppressed, and widespread increases in glucose utilization were seen throughout the brain. Cerebral metabolic activity was increased both in areas rich in dopaminergic receptors, such as the caudate and putamen, and in nondopaminergic areas involved in motor functions. In many structures the rates of glucose utilization in L-dopa-treated parkinsonian monkeys were increased to levels that far exceeded rates measured in normal monkeys. In sharp contrast, similar treatment with L-dopa in normal monkeys had little if any effect on local cerebral glucose utilization. L-Dopa, then, appears to have an action in animals with selective lesions of the substantia nigra pars compacta produced by MPTP that is distinctly different from its effects in the normal monkey.},

  doi          = {10.1073/pnas.84.16.5995},

  url          = {https://www.osti.gov/biblio/5295769},
  journal      = {Proc. Natl. Acad. Sci. U.S.A.; (United States)},
number       = ,

  volume       = 84:16,

  place        = {United States},

  year         = {Sat Aug 01 00:00:00 EDT 1987},

  month        = {Sat Aug 01 00:00:00 EDT 1987}

}

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