Effects of MK-801 upon Local Cerebral Glucose Utilisation in Conscious Rats and in Rats Anaesthetised with Halothane

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Abstract
The effects of MK-801 (0.5 mg/kg i.v.), a noncompetitive N-methyl-d-aspartate (NMDA) antagonist, upon local cerebral glucose utilisation were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilisation with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory–motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothaneanaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus. In the subicular complex, the posterior cingulate cortex, and the mammillary body, the pattern of the metabolic response to MK-801 was reversed with halothane anaesthesia, with significant reductions in glucose use being observed. In the cerebral cortices (particularly the auditory, sensory–motor, and frontal cortex), the decreases in glucose use following MK-801 in anaesthetised animals were qualitatively similar but quantitatively less marked than those in conscious animals. The rates of glucose use in the extrapyramidal and sensory–motor areas, except for the caudate nucleus, were unchanged by the administration of MK-801 in the anaesthetised animals. These data indicate that the functional consequences in vivo of blockade of NMDA receptors are markedly modified by halothane anaesthesia. The divergent responses to MK-801 emphasise the difficulties in the extrapolation of data from anaesthetised rats to conscious rats.