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

Journal Article · Sat Aug 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.16.5995· OSTI ID:5295769

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

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.

• Research Organization: National Institutes of Health, Bethesda, MD (USA)
• OSTI ID: 5295769
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:16; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
BEHAVIOR
BIOLOGICAL EFFECTS
BODY
BRAIN
CARBOHYDRATES
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CEREBRUM
DISEASES
DOPA
DRUGS
GLUCOSE
HEXOSES
HYDROXY ACIDS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
MONKEYS
MONOSACCHARIDES
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHYSIOLOGY
PRIMATES
SACCHARIDES
VERTEBRATES