Chronic levodopa treatment alters basal and dopamine agonist-stimulated cerebral glucose utilization

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Journal of Neuroscience; (USA)

OSTI ID:6213423

Engber, T M; Susel, Z; Kuo, S; Chase, T N ^[1]

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1. National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA)

The effect of chronic levodopa administration on the functional activity of the basal ganglia and its output regions was evaluated by means of the 2-deoxyglucose (2-DG) autoradiographic technique in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The rates of local cerebral glucose utilization were studied under basal conditions as well as in response to challenge with a selective D1 or D2 dopamine-receptor agonist. Levodopa (100 mg/kg/d, i.p.) was administered for 19 d either continuously via infusion with an osmotic pump or intermittently by twice-daily injections. Following a 3-d washout, glucose utilization was found to be decreased by both levodopa regimens in the nucleus accumbens; intermittent levodopa also decreased glucose utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral habenula. In control (lesioned and treated chronically with saline) rats, the D1 agonist SKF 38393 (5 mg/kg, i.v.) increased 2-DG uptake in the substantia nigra pars reticulata and entopeduncular nucleus ipsilateral to the lesion by 84% and 56%, respectively. Both continuous and intermittent levodopa blunted the SKF 38393-induced elevation in glucose metabolism in the substantia nigra pars reticulata, while intermittent levodopa also attenuated the increase in the entopeduncular nucleus. The D2 agonist quinpirole (0.4 mg/kg, i.v.) did not increase glucose utilization in any brain region in control animals; following intermittent levodopa treatment, however, quinpirole increased 2-DG uptake by 64% in the subthalamic nucleus and by 39% in the deep layers of the superior colliculus on the ipsilateral side.

• OSTI ID: 6213423
• Journal Information: Journal of Neuroscience; (USA), Journal Name: Journal of Neuroscience; (USA) Vol. 10:12; ISSN JNRSD; ISSN 0270-6474
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BODY
BRAIN
CARBOHYDRATES
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GLUCOSE
HEXOSES
HYDROXY COMPOUNDS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
METABOLISM
MONOSACCHARIDES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SACCHARIDES
SYMPATHOMIMETICS
VERTEBRATES