Local cerebral glucose utilization in the autoimmune New Zealand Black (NZB) mouse

Summary By means of the [¹⁴C]-2-deoxyglucose method the local cerebral glucose utilization (LCGU) was measured in 41 brain regions in autoimmune New Zealand Black (NZB) mice and in Carworth Farm Winkelmann (CFW) mice, which served as the control strain. At the age of 6 months, the mean LCGU of all measured areas and brain stem nuclei was 67.7 mol glucose/(100 g x min) in the nonautoimmune CFW mice. These LCGU values are within the limits published by other observers. In contrast, in the aged-matched NZB mice the glucose use was markedly reduced, the mean LCGU of all measured areas being 37.7 mol glucose/(100 g x min). These findings suggest that the immunological, morphological and behavioural abnormalities in the aged NZB mouse correlate with a reduced functional activity of the central nervous system, measured as reduced cerebral glucose utilization.     

Local cerebral glucose utilization in the brain of old, learning impaired rats

The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.     

Local cerebral glucose utilization in the brain of old,learning impaired rats

Summary The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [¹⁴C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mol glucose/(100 g × min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.     

Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism

The purpose of the present investigation was to examine the effects of an extract of Ginkgo biloba (EGB) on blood glucose levels, on local cerebral blood flow as well as on cerebral glucose concentration and consumption. The local cerebral blood flow (LCBF) was measured in conscious rats by means of the 14C-iodoantipyrine technique and local cerebral glucose utilization (LCGU) by 14C-2-deoxy-glucose autoradiography. EGB increased the LCBF in 39 analyzed, anatomically defined brain structures by 50 to 100 per cent. No influence of EGB on LCGU was demonstrable. However, EGB enhanced the blood glucose level dose-dependently. Substrates and metabolites of energy metabolism were measured in the cortex of the isolated rat brain perfused at constant rate and with 7 mmol/l glucose added to the perfusion medium. In these experiments EGB decreased the cortical glucose concentration without other substrate levels being changed. These results suggest that glucose uptake may be inhibited by EGB. It is argued that the effects of EGB on brain glucose concentration and blood flow may contribute to its protection of brain tissue against ischemic or hypoxic damage.     

Stimulatory Effect of the D2 Antagonist Sulpiride on Glucose Utilization in Dopaminergic Regions of Rat Brain

Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an "atypical" neuroleptic, is a selective antagonist of D2 dopamine receptors. LCGU was reduced in a few nondopaminergic regions at 1 h after drug administration. Thereafter, SULP progressively elevated LCGU in many other regions. At 3 h, LCGU was elevated in 23% of the regions examined, most of which are related to the CNS dopaminergic system (caudate-putamen, nucleus accumbens, olfactory tubercle, lateral habenula, median eminence, paraventricular hypothalamic nucleus). Increases of LCGU were observed also in the suprachiasmatic nucleus, lateral geniculate, and inferior olive. These effects of SULP on LCGU differ from the effects of the "typical" neuroleptic haloperidol, which produces widespread decreases in LCGU in the rat brain. Selective actions on different subpopulations of dopamine receptors may explain the different effects of the two neuroleptics on brain metabolism, which correspond to their different clinical and behavioral actions.     

Regional Cerebral Glucose Utilization During Insulin-Induced Hypoglycemia in Unanesthetized Rats

Regional cerebral glucose utilization (rCMRgl) was studied during insulin-induced hypoglycemia in unanesthetized rats. Rats were surgically prepared using halothane and nitrous oxide anesthesia and allowed 5 h to recover from the anesthesia before rCMRgl was measured. The rCMRgl was measured using [6-14C]glucose in a normoglycemic control group and two hypoglycemic groups, A (30 min after insulin injection) and B (2 h after insulin injection). The mean plasma glucose level was 7.03 mumol/ml in the normoglycemic group, 1.96 mumol/ml in hypoglycemic group A, and 1.40 mumol/ml in hypoglycemic group B. The rCMRgl in hypoglycemic group A decreased 8-18% in 17 brain regions measured; five changes were statistically significant. The rCMRgl in hypoglycemic group B decreased significantly in all but one of the brain regions measured; the decrease ranged from 15% in the pyramidal tract to 36% in the motor and auditory cortices. The rCMRgl in every brain region decreased when the plasma glucose level fell below 1.5-2.5 mumol/ml. No brain region could maintain rCMRgl at plasma glucose concentrations lower than predicted by regional glucose influx described in previous studies. Glucose utilization in all brain regions appears to be limited by the influx of glucose.     

Determination of glucose turnover in sea bass Dicentrarchus labrax. Comparative aspects of glucose utilization

1. Parameters of in vivo glucose utilization by sea bass (132 +/- 6 g, mean +/- SEM) acclimated at 15 degrees C in sea-water were measured after single injection of labelled glucose. 2. Glucose turnover rate (RG; mumol . min-1 . kg-1) was found to be 0.55-065 (2-3H glucose) and 0.34 +/- 0.42 (U14C glucose). 3. Glucose transit time was 443-449 min, glucose mass 233-261 mumol . kg-1, and glucose recycling 37%. 4. Oxygen consumption (MO2) amounted to 94 +/- 6.2 mumol . min-1 . kg-1. 5. The comparison with other fish species, mammals and birds, taking into account body size, temperature, diet, exercise, in poikilotherms and homeotherms leads to the calculation of a glucose turnover index (RGI = RG x 6 x 100 x MO2(-1)). 6. Value of this, generally lower in ectotherm teleosts (2-9), than in endotherms: mammals, birds and thunidae (22-60), confirms the minor quantitative importance of glucose in the metabolism of most fish.     

The effects of fluorocitrate on renal glutamine, lactate, alanine, and oxygen metabolism in the dog

Acid-base status is considered the major factor controlling renal NH4+ production from glutamine, with maximal values found in chronic acidosis. However, metabolic inhibitors have been shown to increase NH4+ production without acid-base change; the mechanism for this increase is unclear. Fluorocitrate was administered to dogs with chronic metabolic alkalosis. Following fluorocitrate total renal NH4+ production rose from 32 +/- 5 to 104 +/- 15 mumol/(min.100 mL glomerular filtration rate (GFR] (p less than 0.01) and glutamine extraction rose from 26 +/- 8 to 65 +/- 8 mumol/(min.100 mL GFR) (p less than 0.01). These values approximate maximal values found in chronic acidosis. Lactate utilization fell from 165 +/- 19 to 99 +/- 7 mumol/(min.100 mL GFR) following fluorocitrate (p less than 0.01). Citrate extraction fell to zero and alanine production rose from 27 +/- 4 to 46 +/- 7 mumol/(min.100 mL GFR) (p less than 0.01). Oxygen consumption remained unchanged following fluorocitrate, 584 +/- 29 vs. 549 +/- 29 mumol/(min.100 mL GFR). These results demonstrate that in the presence of metabolic inhibition in the kidney, ATP production remains constant. This is achieved by increased utilization of one substrate, glutamine, when the ATP production from other substrates is reduced. Thus the necessity to maintain constant ATP production appears to modulate renal NH4+ production.     

N omega-nitro-L-arginine influences cerebral metabolism in awake sheep.

Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor-nitric oxide (NO). An inhibitor of NO formation, N omega-nitro-L-arginine (LNA, 100 micrograms/kg i.v.), was given to conscious sheep (n = 6) during normoxia and again in hypocapnic hypoxia (arterial PO2 approximately 38 Torr). Blood samples were obtained from the aorta and sagittal sinus, and cerebral blood flow (CBF) was measured with 15-microns radiolabeled microspheres. During normoxia, LNA elevated (P < 0.05) mean arterial pressure from 82 +/- 3 to 88 +/- 2 (SE) mmHg and cerebral perfusion pressure (CPP) from 72 +/- 3 to 79 +/- 3 mmHg, CBF was unchanged, and cerebral lactate release (CLR) rose temporarily from 0.0 +/- 1.9 to 13.3 +/- 8.7 mumol.min-1 x 100 g-1 (P < 0.05). The glucose-O2 index declined (P < 0.05) from 1.67 +/- 0.16 to 1.03 +/- 0.4 mumol.min-1 x 100 g-1. Hypoxia increased CBF from 59.9 +/- 5.4 to 122.5 +/- 17.5 ml.min-1 x 100 g-1 and the glucose-O2 index from 1.75 +/- 0.43 to 2.49 +/- 0.52 mumol.min-1 x 100 g-1 and decreased brain CO2 output, brain respiratory quotient, and CPP (all P < 0.05), while cerebral O2 uptake, CLR, and CPP were unchanged. LNA given during hypoxia decreased CBF to 77.7 +/- 11.8 ml.min-1 x 100 g-1 and cerebral O2 uptake from 154 +/- 22 to 105.2 +/- 12.4 mumol.min-1 x 100 g-1 and further elevated mean arterial pressure to 98 +/- 2 mmHg (all P < 0.05), CLR was unchanged, and, surprisingly, brain CO2 output and respiratory quotient were reduced dramatically to negative values (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Principles of the 2-deoxyglucose method for the determination of the local cerebral glucose utilization

Sokoloff and co-workers developed the 2-deoxy-D-[1-14C]glucose (2DG) method in order to study the local cerebral glucose utilization (LCGU) of discrete brain regions in vivo. Energy metabolism of the adult mammalian brain is almost entirely dependent on glucose. The majority of the glucose taken up by the brain is needed for the maintenance of the membrane potentials and the electrical activity. The functional activity could thus be shown to be closely linked to energy metabolism. Consequently, examination of the energy metabolism by measuring the cerebral metabolic rate for glucose can provide information concerning functional activity in all of the neuroanatomically defined regions of the brain. Studying the fate of experimentally injected 2-deoxy-D-[1-14C]glucose, a radioactive labeled analogue of glucose, and, subsequently, employing quantitative autoradiographic techniques, it is possible to estimate the levels of the local cerebral glucose utilization in specific regions of the brain. According to Sokoloff (1982) the LCGU represents a "metabolic encephalography".     

Local cerebral glucose utilization in the hippocampus of old rats

Summary The local cerebral glucose utilization (LCGU) was measured in the different areas and layers of the Ammon's horn and dentate gyrus of young adult (3 to 4-month-old) rats, and of 27-month-old rats with proven cognitive deficits. The LCGU was determined by quantitative [¹⁴C]2-deoxyglucose autoradiography. Compared to young animals, in the old rats the LCGU was significantly reduced by 12% to 15% in the oriens layers of CA1 and CA2, the pyramidal layers of the CA sectors 1–3, the radiatum and lacunosum-molecular layers of CA2 and CA3 and in the lucidum layer of CA3. The LCGU values of all the other layers of the Ammon's horn and the dentate gyrus did not differ significantly between young and old rats. The pattern of the LCGU reduction found in the old rats roughly resembles changes found after fimbra-fornix lesions or systemic administration of scopolamine, suggesting a functionally important deficit in the cholinergic innervation of the old rats' hippocampi.     

Growth hormone and IGF-I modulate local cerebral glucose utilization and ATP levels in a model of adult-onset growth hormone deficiency

Decreases in plasma IGF-I levels that occur with age have been hypothesized to contribute to the genesis of brain aging. However, support for this hypothesis would be strengthened by evidence that growth hormone (GH)/IGF-I deficiency in young animals produces a phenotype similar to that found in aged animals. As a result, we developed a unique model of adult-onset GH/IGF-I deficiency by using dwarf rats specifically deficient in GH and IGF-I. The deficiency in plasma IGF-I is similar to that observed with age (e.g., 50% decrease), and replacement of GH restores levels of IGF-I to that found in young animals with normal GH levels. The present study employs this model to investigate the effects of circulating GH and IGF-I on local cerebral glucose utilization (LCGU). Analysis of LCGU indicated that GH/IGF-I-deficient animals exhibit a 29% decrease in glucose metabolism in many brain regions, especially those involved in hippocampally dependent processes of learning and memory. Similarly, a high correlation between plasma IGF-I levels and glucose metabolism was found in these areas. The deficiency in LCGU was not associated with alterations in GLUT1, GLUT3, or hexokinase activity. A 15% decrease in ATP levels was also found in hippocampus of GH-deficient animals, providing compelling data that circulating GH and IGF-I have significant effects on the regulation of glucose utilization and energy metabolism in the brain. Furthermore, our results provide important data to support the conclusion that deficiencies in circulating GH/IGF-I contribute to the genesis of brain aging.     

Local cerebral glucose utilization in the hippocampus of old rats

The local cerebral glucose utilization (LCGU) was measured in the different areas and layers of the Ammon's horn and dentate gyrus of young adult (3 to 4-month-old) rats, and of 27-month-old rats with proven cognitive deficits. The LCGU was determined by quantitative [14C]2-deoxyglucose autoradiography. Compared to young animals, in the old rats the LCGU was significantly reduced by 12% to 15% in the oriens layers of CA1 and CA2, the pyramidal layers of the CA sectors 1-3, the radiatum and lacunosum-molecular layers of CA2 and CA3 and in the lucidum layer of CA3. The LCGU values of all the other layers of the Ammon's horn and the dentate gyrus did not differ significantly between young and old rats. The pattern of the LCGU reduction found in the old rats roughly resembles changes found after fimbra-fornix lesions or systemic administration of scopolamine, suggesting a functionally important deficit in the cholinergic innervation of the old rats' hippocampi.     

Brain injury: New insights into neurotransmitter and receptor mechanisms

The studies reviewed here represent a continuing search for mechanisms which play a role in neurological disturbances resulting from brain injury. Focal cortical freezing lesions in rats were shown to cause a widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere and this was interpreted as reflecting a depression of cortical activity. Such an interpretation was supported by the finding that in lesioned brain reduction of cerebral metabolism by pentobarbital and isoflurane was limited by the metabolic depression that has already occurred as a result of injury and by the demonstration that the energy status and substrate (glucose) supply in the cortical areas in the injured brain have not been compromised at the time when LCGU was decreased. Both the serotonergic and the noradrenergic neurotransmitter systems were implicated in functional alterations associated with injury. Cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere and complete inhibition of 5-HT synthesis withp-chlorophenylalanine ameliorated the decrease in cortical LCGU, interpreted as reflecting cortical functional depression. Cortical norepinephrine metabolism was bilaterally increased in focally injured brain, while prazosin, a selective ₁-noradrenergic receptor blocker, normalized cortical LCGU in the lesioned hemisphere. Low-affinity in vivo binding of [¹²⁵I]HEAT, another selective ₁-receptor ligand, was specifically increased in cortical areas of the lesioned hemisphere at the time of the greatest depression in LCGU, suggesting that ₁-adrenoreceptors may be of functional importance in injured brain. The general conclusion from this series of studies on mechanisms underlying functional disturbances in injured brain is that both the serotonergic and the noradrenergic neurotransmitter systems are involved in the widespread cortical depression which develops with time as a consequence of a focal lesion. The data are compatible with the inhibitory effects of NE and 5-HT in the cortex and with the hypothesis that these two transmitter systems affect cortical information processing.     

Local Cerebral Glucose Utilization in Two Models of B12 Deficiency

Local cerebral glucose utilization (LCGU), as measured by the 2-deoxy-D-[1-14C]glucose technique, reflects local cerebral functional activity. In an effort to elucidate mechanisms of the encephalopathy associated with deficiency of vitamin B12, LCGU was determined in two recently described models of effective B12 deficiency: exposure of rats to subanesthetic doses of nitrous oxide (N2O) and/or administration of 1-amino-cyclopentane-1-carboxylic acid (cycloleucine). Our results show that exposure of adult rats to N2O depresses LCGU selectively in cortical, auditory, and limbic structures, in association with a depression in whole-brain activities of the vitamin B12-dependent methyltetrahydrofolate-homocysteine methyl-transferase (EC 2.1.1.13, methionine synthetase). Cycloleucine has no discernible effect on LCGU in the adult rat and does not change the cerebral activity of methionine synthetase.     

Methylene blue inhibits hypoxic cerebral vasodilation in awake sheep.

Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor-nitric oxide. Methylene blue (MB), an in vitro inhibitor of soluble guanylate cyclase, was injected intravenously into six adult ewes instrumented chronically with left ventricular, aortic, and sagittal sinus catheters. In normoxia, MB (0.5 mg/kg) did not alter cerebral blood flow (CBF, measured with 15-microns radiolabeled microspheres), cerebral O2 uptake, mean arterial pressure (MAP), heart rate, cerebral lactate release, or cerebral O2 extraction fraction (OEF). After 1 h of normobaric poikilocapnic hypoxia (arterial PO2 40 Torr, arterial O2 saturation 50%), CBF increased from 51 +/- 5.8 to 142 +/- 18.8 ml.min-1 x 100 g-1, cerebral O2 uptake from 3.5 +/- 0.25 to 4.7 +/- 0.41 ml.min-1 x 100 g-1, cerebral lactate release from 2 +/- 10 to 100 +/- 50 mumol.min- x 100 g-1, and heart rate from 107 +/- 5 to 155 +/- 9 beats/min (P < 0.01). MAP and OEF were unchanged from 91 +/- 3 mmHg and 48 +/- 4%, respectively. In hypoxia, 30 min after MB (0.5 mg/kg), CBF declined to 79.3 +/- 11.7 ml.min-1 x 100 g-1 (P < 0.01), brain O2 uptake (4.3 +/- 0.9 ml.min-1 x 100 g-1) and heart rate (133 +/- 9 beats/min) remained elevated, cerebral lactate release became negative (-155 +/- 60 mumol.min-1 x 100 g-1, P < 0.01), OEF increased to 57 +/- 3% (P < 0.01), and MAP (93 +/- 5 mmHg) was unchanged. The sheep became behaviorally depressed, probably because of global cerebral ischemia. These results may be related to interference with a guanylate cyclase-dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasmodium yoelii: blood oxygen and brain function in the infected mouse

The carriage of oxygen by the blood and the in vivo response of the brain were investigated in mice infected with a lethal strain of Plasmodium yoelii. All mice with parasitaemia exceeding 70% were severely anaemic (Hb 3.5 +/- 1.8 g/dl; mean +/- 1 SD), acidotic (blood pH 7.04 +/- 0.06) and hypoglycaemic (blood glucose 0.6 +/- 0.76 mumol/ml). The oxyhaemoglobin dissociation curve (ODC) of blood from heavily infected mice was shifted right as compared to controls, but the increase in p50 was less than expected from the accompanying acidosis. The reduced shift right was due to a decrease in the 2,3-DPG/Hb ratio in infected animals (0.72 +/- 0.12, n = 17 vs 1.10 +/- 0.09, n = 12 in controls). Despite the severity of terminal infection, the cerebral pH and the relative steady-state concentrations of PCr, ATP and Pi measured in vivo by nuclear magnetic resonance (31P NMR) were normal. Alterations in brain energy status and pH cannot account for cerebral signs or death in this proposed mouse model of cerebral malaria.     

The estimation of rates of utilization of glucose and ketone bodies in the brain of the suckling rat using compartmental analysis of isotopic data

The brains of 18-day-old rats utilize glucose and ketone bodies. The rates of acetyl-CoA formation from these substrates and of glycolysis were determined in vivo from the labelling of intermediary metabolites after intraperitoneal injection of d-[2-(14)C]glucose, l(+)-[3-(14)C]- and l(+)-[U-(14)C]-lactate and d(-)-3-hydroxy[(14)C]butyrate. Compartmental analysis was used in calculating rates to allow for the rapid exchange of blood and brain lactate, the presence in brain of at least two pools each of glucose and lactate, and the incomplete equilibration of oxaloacetate with aspartate and of 2-oxoglutarate with glutamate. Results were as follows. 1. Glucose and ketone bodies labelled identical pools of tricarboxylate-cycle metabolites, and were in every way alternative substrates. 2. The combined rate of oxidation of acetyl-CoA derived from pyruvate (and hence glucose) and ketone bodies was 1.05mumol/min per g. 3. Ketone bodies contributed 0.11-0.53mumol/min per g in proportion to their concentration in blood, with a mean rate of 0.30mumol/min per g at 1.24mm. 4. Pyruvate and ketone bodies were converted into lipid at 0.018 and 0.008mumol/min per g respectively. 5. Glycolysis, at 0.48mumol/min per g, was more rapid in most rats than pyruvate utilization by oxidation and lipid synthesis, resulting in a net output of lactate from brain to blood. 6. Rates of formation of brain glutamate, glutamine and aspartate were also measured. Further information on the derivation of the models has been deposited as Supplementary Publication SUP 50034 (18 pages) at the British Library, Lending Division (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7QB, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5.     

Improvement of impaired postoperative insulin action by bradykinin

The effect of bradykinin on insulin-stimulated glucose metabolism was studied in 5 operated patients using the euglycemic insulin clamp technique and the forearm catheter technique. Insulin infusion [1.0 mU/(kg b.w. X min)] raised plasma insulin levels up to 73 muU/ml. Euglycemia was maintained by a computerized glucose infusion rate, amounting to 2.9 mg/(kg b.w. X min). Addition of bradykinin [1.5 micrograms/(kg b.w. X h)] resulted in a significant increase of the glucose infusion rate [+ 1.0 mg/(kg b.w. X min)] indicating elevated whole body glucose uptake. This was related to an enhanced forearm glucose uptake [+ 1.16 mumol/(100 g X min)]. Forearm blood flow remained stable.     

Effect of the Non-NMDA Receptor Antagonist, 2,3-Dihydro-6-Nitro-7-Sulfamoylbenzo(f)quinoxaline, on Local Cerebral Glucose Uptake in the Limbic Forebrain

Abstract: The present investigation examined the effect of in vivo antagonism of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor by 2,3-dihydro-6-nitro-7-sulfamoylbenzo( f )quinoxaline (NBQX) on local cerebral glucose utilization (LCGU) using the quantitative autoradiographic Pdeoxy[¹⁴C]-glucose method in conscious rats. NBQX, at doses of 10, 30, and 60 mg/kg i.p. or three injections of 30 mg/kg i.p., did not increase LCGU in limbic areas such as the primary olfactory cortex. olfactory tubercle, hippocampus, dentate gyrus, posterior cingulate cortex, mamillary body, caudate nucleus, anterior thalamic nucleus, and nucleus accumbens. NBQX, at doses of 260 mg/kg i.p., decreased LCGU in these brain areas. These data demonstrate that in vivo antagonism of the AMPA receptors by NBQX produces a pattern of alterations in metabolic activity, different from that produced by noncompetitive antagonists of the N-methyl-D-aSpartate (NMDA) receptor, e.g., phencyclidine and MK-801. Combined with a lack of "phencyclidine-like" behavior produced by NBQX. these data suggest that antagonism of the AMPA receptor represents a novel mechanism to block excitatory amino acids in the CNS, which may be devoid of unwanted behavioral side effects associated with noncompetitive antagonism of the NMDA receptor.