Local Cerebral Metabolic Effects of L-Dopa Therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in Monkeys

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 16; pp. 5995 - 5999
• Main Authors: Porrino, Linda J., Burns, Richard S., Crane, Alison M., Palombo, Ernesta, Kopin, Irwin J., Sokoloff, Louis
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1987; National Acad Sciences
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Blood plasma; Brain - drug effects; Brain - metabolism; Dosage; Female; Globus pallidus; Glucose - metabolism; Intravenous injections; Levodopa - therapeutic use; Macaca mulatta; Male; Medical sciences; Metabolism; Neuropharmacology; Parkinson disease; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - drug therapy; Parkinsonian disorders; Pharmacology. Drug treatments; Pyridines; Receptors; Substantia nigra; Thalamus; Tissue Distribution; Brain; Nervous system diseases; Monkey; Parkinson disease; Patient; Glucose; Metabolism; Normal; Antiparkinson agent; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Animal; Primates; Dopa; Comparative study
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.16.5995

The quantitative 2-deoxy[14C]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 (100 mg with 10 mg carbidopa) 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-dopatreated 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.