Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

Journal Article · Mon Apr 01 00:00:00 EST 1991 · Synapse (New York); (United States)

DOI:https://doi.org/10.1002/syn.890070403· OSTI ID:5556823

Clow, D W; Lee, S J; Hammer, Jr, R P ^[1]

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1. Department of Anatomy and Reproductive Biology, School of Medicine, University of Hawaii, Honolulu (USA)

The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative {sup 14}C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions.

• OSTI ID: 5556823
• Journal Information: Synapse (New York); (United States), Vol. 7:4; ISSN 0887-4476
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
RECEPTORS
ENZYME INHIBITORS
BIOCHEMICAL REACTION KINETICS
GLUCOSE
METABOLISM
ANTICONVULSANTS
AUTORADIOGRAPHY
CARBON 14 COMPOUNDS
CEREBRAL CORTEX
DOSE-RESPONSE RELATIONSHIPS
RATS
ALDEHYDES
ANIMALS
BODY
BRAIN
CARBOHYDRATES
CARBON COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CEREBRUM
DRUGS
HEXOSES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MONOSACCHARIDES
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RODENTS
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
550501 - Metabolism- Tracer Techniques