Significant Increase In Glucose Utilization Research Articles

Antidiabetic and Anticancer Potentials of Mangifera indica L. from Different Geographical Origins.

Mango fruit is well known for its nutritional and health benefits due to the presence of a plethora of phytochemical classes. The quality of mango fruit and its biological activities may change depending upon the variation in geographical factors. For the first time, this study comprehensively screened the biological activities of all four parts of the mango fruit from twelve different origins. Various cell lines (MCF7, HCT116, HepG2, MRC5) were used to screen the extracts for their cytotoxicity, glucose uptake, glutathione peroxidase activity, and α-amylase inhibition. MTT assays were carried out to calculate the IC50 values for the most effective extracts. The seed part from Kenya and Sri Lanka origins exhibited an IC50 value of 14.44 ± 3.61 (HCT116) and 17.19 ± 1.60 (MCF7). The seed part for Yemen Badami (119 ± 0.08) and epicarp part of Thailand (119 ± 0.11) mango fruit showed a significant increase in glucose utilization (50 μg/mL) as compared to the standard drug metformin (123 ± 0.07). The seed extracts of Yemen Taimoor seed (0.46 ± 0.05) and Yemen Badami (0.62 ± 0.13) produced a significant reduction in GPx activity (50 μg/mL) compared to the control cells (100 μg/mL). For α-amylase inhibition, the lowest IC50 value was observed for the endocarp part of Yemen Kalabathoor (108.8 ± 0.70 μg/mL). PCA, ANOVA, and Pearson's statistical models revealed a significant correlation for the fruit part vs. biological activities, and seed part vs. cytotoxicity and α-amylase activity (p = 0.05). The seed of mango fruit exhibited significant biological activities; hence, further in-depth metabolomic and in vivo studies are essential to effectively utilize the seed part for the treatment of various diseases.

Toll like receptor mediated immune stimulation can be visualized in vivo by [18F]FDG-PET

IntroductionHigh uptake of [18F]-2-fluorodeoxyglucose ([18F]FDG) by inflammatory cells is a frequent cause of false positive results in [18F]FDG-positron-emission tomography (PET) for cancer diagnostics. Similar to cancer cells, immune cells undergo significant increases in glucose utilization following activation, e.g., in infectious diseases or after vaccination during cancer therapy. The aim of this study was to quantify certain immune effects in vitro and in vivo by [18F]FDG-PET after stimulation with TLR ligands and specific antibodies. MethodsIn vivo [18F]FDG-PET/magnetic resonance imaging (MRI) and biodistribution was performed with C57BL/6 mice immunized with CpG or LPS. Cellular [18F]FDG-uptake assays were performed with B cells and T cells or with whole spleen cells after stimulation with CpG, LPS and anti-CD3/CD28. In vitro and in vivo activation of B and T cells was examined by concomitant FACS analysis to correlate immune cell activation with the strength of [18F]FDG accumulation. ResultsWe could show that TLR mediated activation of B cells increases [18F]FDG uptake, and that B cells show faster kinetics and greater effect than T cells stimulated by the CD3/CD28 pathway. In the whole spleen cell population the [18F]FDG signal was triggered mainly by the activation of B cells, corresponding closely to expression of typical stimulation markers. This finding could also been seen in vivo in [18F]FDG-PET/MRI, where the spleen was clearly visible after TLR stimulation and B cells showed upregulation of CD80 and CD86. ConclusionIn vivo TLR stimulation can be visualized by increased [18F]FDG uptake in lymphoid organs. The signal generated in the spleen after immunization might be mainly attributed to the activation of B cells within. Advances in Knowledge and Implications for Patient CareKnowledge of the composition of cells that take up [18F]FDG during vaccination or in response to therapy may improve successful treatment of cancer patients in the future.

In vivo mouse model for examining contribution of inflammation to development of obesity and diabetes

An adipose tissue‐mediated shift to production of proinflammatory cytokines in obesity likely contributes to the low‐level systemic inflammation that is seen in metabolic syndrome‐associated chronic pathologies such as diabetes. The mechanism explaining this relationship remains unknown. In this study, we present specific details on using pharmacological supplementation with triptolide, a diterpene triepoxide with anti‐inflammatory and immunosuppressive properties, to diet‐induced obese (DIO) C57BL/6J male mice. Animals received 50 ug/kg of triptolide in corn oil (vehicle) via oral gavage every 3 d for 9 wk and underwent oral glucose tolerance test on wk 1 (baseline), wk 7 and wk 9. Significant increase in glucose utilization and improved insulin sensitivity were associated with triptolide in the absence of the direct effects on obesity measures of food intake, body weight, or composition. Macrophage recruitment and cytokine signature of the adipose tissue were significantly reduced by triptolide with minimal or no effect on the adipose humoral factors leptin and adiponectin. These data demonstrate that DIO‐triptolide mouse is a tractable animal model for the study of obesity‐related metabolic dysfunction and chronic inflammation. The study was supported in part by the 5P50AT002776‐05 grant from NCCAM.

Improved Metabolic Stimulus for Glucose-Induced Insulin Secretion through GK and PFK-2/FBPase-2 Coexpression in Insulin-Producing RINm5F Cells

The glucose sensor enzyme glucokinase plays a pivotal role in the regulation of glucose-induced insulin secretion in pancreatic beta-cells. Activation of glucokinase represents a promising concept for the treatment of type 2 diabetes. Therefore, we analyzed the glucokinase activation through its physiological interaction partner, the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) and the resulting effect on glucose metabolism in insulin-producing cells. In RINm5F-GK-PFK-2/FBPase-2 cells stably overexpressing glucokinase plus islet PFK-2/FBPase-2, colocalization between both enzymes as well as elevation of glucokinase activity were significantly increased at a stimulatory glucose concentration of 10 mmol/liter. RINm5F-GK-PFK-2/FBPase-2 cells showed under this culture condition a significant increase in glucose utilization and in the ATP/ADP ratio compared with RINm5F-GK cells, which only overexpress glucokinase. Also glucose-induced insulin secretion was elevated in RINm5F-GK-PFK-2/FBPase-2 cells in comparison to RINm5F-GK cells. Furthermore, pyruvate accumulation and lactate production in RINm5F-GK-PFK-2/FBPase-2 cells were significantly lower at both 10 and 30 mmol/liter glucose than in RINm5F-GK and RINm5F cells. The significant improvement of glucose metabolism after PFK-2/FBPase-2 overexpression is apparently not exclusively the result of high glucokinase enzyme activity. Stabilization of the closed glucokinase conformation by PFK-2/FBPase-2 may not only activate the enzyme but also improve metabolic channeling in beta-cells.

In vivo induction of insulin secretion by ornithine α-ketoglutarate: Involvement of nitric oxide and glutamine

We previously demonstrated that ornithine α-ketoglutarate (OKG), known for its anabolic properties, induces insulin secretion in vitro. The present study was undertaken to further characterize this effect in vivo and investigate a possible interaction with glucose both in vivo and in vitro. Male Wistar rats received an intravenous bolus of OKG (25 mg/kg) and/or glucose (0.8 g/kg) or saline, and their plasma insulin and glucose levels were monitored for 30 minutes. OKG alone increased plasma insulin to a similar extent to glucose. In combination with glucose, OKG significantly increased glucose-induced insulin secretion in vivo and in vitro, and led to a significant increase in glucose utilization in vivo. The absence of significant variations in plasma arginine and glutamine suggests a direct effect of OKG on the pancreas. To assess the involvement of the synthesis of nitric oxide and glutamine in OKG-induced insulin secretion, the experiments were repeated in the presence of inhibitors of these 2 pathways, respectively L-nitroarginine-methylester (L-NAME) and methionine sulfoximine (MSO). Both inhibitors were able significantly to reduce OKG-induced insulin secretion without affecting either basal or glucose-induced insulin release. Thus OKG acts directly with glucose on islets to induce insulin secretion via mechanisms involving NO and glutamine synthesis. In addition, our results suggest that OKG and glucose act via separate pathways. Copyright 2003, Elsevier Science (USA). All rights reserved.

Local injection of antisense oligonucleotides targeted to the glial glutamate transporter GLAST decreases the metabolic response to somatosensory activation.

The mechanisms responsible for the local increase in brain glucose utilization during functional activation remain unknown. Recent in vitro studies have identified a new signaling pathway involving an activation of glial glutamate transporters and enhancement of neuron-astrocyte metabolic interactions that suggest a putative coupling mechanism. The aim of the present study was to determine whether one of the glutamate transporters exclusively expressed in astrocytes, GLAST, is involved in the neurometabolic coupling in vivo. For this purpose, rats were microinjected into the posteromedial barrel subfield (PMBSF) of the somatosensory cortex with GLAST antisense or random phosphorothioate oligonucleotides. The physiologic activation was performed by stimulating the whisker-to-barrel pathway in anesthetized rats while measuring local cerebral glucose utilization by quantitative autoradiography in the PMBSF. Twenty-four hours after injection of two different antisense GLAST oligonucleotide sequences, and despite the presence of normal whisker-related neuronal activity in the PMBSF, the metabolic response to whisker stimulation was decreased by more than 50%. Injection of the corresponding random sequences still allowed a significant increase in glucose utilization in the activated area. The present study highlights the contribution of astrocytes to neurometabolic coupling in vivo. It provides evidence that glial glutamate transporters are key molecular components of this coupling and that neuronal glutamatergic activity is an important determinant of energy utilization. Results indicate that astrocytes should also be considered as possible sources of altered brain metabolism that could explain the distinct imaging signals observed in some pathologic situations.

Brain sites involved in δ-opioid receptor-mediated actions

The brain sites which may be involved in δ-opioid receptor agonist-mediated actions in vivo were examined using quantitatiev [1- 14C]deoxyglucose autoradiography. For this purpose [D-Pen 2,D-Pen 5]enkephaline (DPDPE) - one of the most selective δ-opioid receptor agonist available - was employed. DPDPE was most effective at a dose of 25 μg i.c.v. All of the motor regions measured displayed significant increases in glucose utilization. Further, increases were widespread in limbic forebrain regions and were also detected in components of the limbic midbrain. The ventroposterolateral thalamic nuclues, a region relaying somatosensory information to the cerebral cortex, displayed the strongest enhancement of glucose utilization. This regional pattern of changes is assumed to underlie the modulatory role in the processing of somatosensory and nociceptive information of DPDPE, its rewarding properties and the behabioral arousal produced by the δ-opioid agonist. A selective involvement of δ-opioid receptors in these effects was indicated by their antagonism by the δ-opioid receptor antagonist ICI 174,865 ( N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH).

Anaerobic glycolysis preceding white-matter destruction in experimental neonatal hydrocephalus.

The metabolic changes in neonatal hydrocephalus that lead to permanent brain injury are not clearly defined, nor is the extent to which these changes can be prevented by a cerebrospinal fluid shunt. To clarify these processes, cerebral glucose utilization was examined using [14C]2-deoxyglucose autoradiography in 1-month-old kittens, kaolin-induced hydrocephalic littermates, and hydrocephalic kittens in which a ventriculoperitoneal shunt had been inserted 10 days after kaolin injection. The hydrocephalic kittens showed thinning of the cerebral mantle and an anterior-to-posterior gradient of enlargement of the ventricular system, with a ventricle:brain ratio of 24% for the frontal and 35% for the occipital horns compared with control (< 0.5%) and shunted (< 5%) animals. White matter in hydrocephalic animals was edematous. Myelination was delayed in the periventricular region and in the cores of the cerebral gyri. Glucose utilization in hydrocephalic and shunted animals was unchanged from control animals in all gray-matter regions examined. However, in hydrocephalic animals, the frontal white matter exhibited a significant increase in glucose utilization (25 mumol.100 gm-1.min-1) in the cores of gyri compared with normal surrounding white-matter values (14.8 mumol.100 gm-1.min-1). Very low values (mean 4 mumol.100 gm-1.min-1) were found in areas corresponding to severe white-matter edema, and these areas were surrounded by a halo of increased activity (24 mumol.100 gm-1.min-1). In contrast, cytochrome oxidase activity in white matter was homogeneous. Shunting resulted in restoration of the cerebral mantle thickness, a return to normal levels of glucose utilization in the white matter, and an improvement in myelination. It is suggested that the areas of increased glucose utilization seen in the white matter represent anaerobic glycolysis which, if untreated, progresses to infarction. The pattern of this increased glucose utilization matches that of expected myelination and, during this period of high energy demand, white matter may be susceptible to the hypoperfusion associated with hydrocephalus.

Benfluorex normalizes hyperglycemia and reverses hepatic insulin resistance in STZ-induced diabetic rats.

We have examined the effect of chronic (20 days) oral administration of benfluorex (35 mg/kg) in a rat model of NIDDM, induced by injection of STZ 5 days after birth and characterized by frank hyperglycemia, hypoinsulinemia, and hepatic and peripheral insulin resistance. We assessed the following: 1) basal blood glucose and insulin levels, 2) glucose tolerance and glucose-induced insulin release in vivo and in vitro, and 3) basal and insulin-stimulated in vivo glucose production and glucose utilization, using the insulin-clamp technique in conjunction with isotopic measurement of glucose turnover. The in vivo insulin response of several individual tissues also was evaluated under the steady-state conditions of the clamp, using the uptake of the glucose analogue 2-deoxy-D-glucose as a relative index of glucose metabolism. In the benfluorex-treated diabetic rats, postabsorptive basal plasma glucose levels were decreased (8.1 +/- 0.2 mM compared with 10.5 +/- 0.5 mM in the pair-fed untreated diabetic rats and 6.1 +/- 0.2 mM in the benfluorex-treated nondiabetic rats), whereas the basal and glucose-stimulated intravenous glucose tolerance test plasma insulin levels were not improved. Such a lack of improvement in the glucose-induced insulin release after benfluorex treatment was confirmed under in vitro conditions (perfused pancreas). In the pair-fed untreated diabetic rats, the basal glucose production and overall glucose utilization were significantly increased, and during hyperinsulinemia both liver and peripheral tissues revealed insulin resistance. In the benfluorex-treated diabetic rats, the basal glucose production and basal overall glucose utilization were normalized. After hyperinsulinemia, glucose production was normally suppressed, whereas overall glucose utilization was not significantly improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of cocaine interaction with delta-9-tetrahydrocannabinol on glucose metabolism in the rat testis

In this study, the characteristics of cocaine (COC) interaction with delta-9-tetrahydrocannabinol (THC) on glucose metabolism in the rat testis were investigated at different time points. Rats receiving 20 mg/kg IP COC at 0830 h and sacrificed at 15 min, 30 min and 60 min posttreatment showed no change in glucose metabolism. Moreover, 5 mg/kg, IV, COC treatment at 0900 h to rats and sacrificed 60 min postexposure, also produced no change in glucose metabolism. However, at 1300 h, the same protocol with IV COC treatment resulted in a significant increase in glucose utilization by the testis. Furthermore, a THC dose of 10 mg/kg, PO to the rats at 0830 or at 1130 h, followed by sacrifice 90 min later caused a significant decrease in glucose utilization at both time points. Similarly, when rats were given both THC and COC (THC at 0830 h, COC 90 min later) and sacrificed 60 min post-COC, it resulted in a further decrease in testicular glucose metabolism as compared to the rats treated by THC alone. On the other hand, concurrent exposure of rats to these drugs at 1300 h with same protocol, ended up with no change in glucose utilization in the testis. These data suggest that not only the route of administration but also the time of exposure plays an important role in defining the nature of the effects of COC/THC interaction on rat testicular glucose metabolism.

Regional changes in spinal cord glucose metabolism in a rat model of painful neuropathy

Spinal cord patterns of metabolic activity in a model of neuropathic pain were assessed in unanesthtized rats by the [ 14C]-2-deoxyglucose (2-DG) technique. Rats used in this procedure had demonstrable thermal hyperalgesia ipsilateral to sciatic nerve ligation and ipsilateral hind-paws that were lifted in a guarded position. The latter indicated possible spontaneous pain. Sciatic nerve ligation produced significant increases in glucose utilization in the dorsal and ventral horns of both sides, with greater activity present on the ipsilateral as compared to the contralateral side. Peak activity was in laminae V–VI, a region involved in nociceptive processing. Thus, a chronic increase in neuronal activity in these regions may reflect spontaneous neuropathic pain.

Evolution of Insulin Secretory Response to Glucose by Perifused Islets From Lean (FA/FA) Rats Chronically Infused With Glucose

Chronic infusion of nondiabetic rats with glucose for up to 7 days modified the insulin secretory response by subsequently perifused islets. Thus, on the 1st day of infusion with 40% glucose, the islets responded to 16.7 mM glucose with a 3.9-fold increase in insulin release during the first 10 min with no significant change during the second-phase insulin output compared with the control group. On the 2nd day, there was a 2-fold enhancement of insulin release during the initial 10 min of stimulation, the second phase being a similar to control islets. On the 5th day of infusion, the pattern of insulin release was not significantly different from the control group. After 7 day of infusion, there was a 46% decrease in first-phase and a 33% decrease in second-phase insulin response to glucose. The response to 10 mM arginine plus 5 mM glucose was not modified by chronic glucose infusion. Priming experiments indicate that islets from rats infused for 7 days were not able to recover the normal pattern of secretion in vitro. Islets from 7-day glucose-infused rats contained 75% more protein and had a significantly higher insulin content than control islet, suggesting that insulin synthesis is not involved in the loss of the response observed. Glucose metabolism by the islets was modified by glucose infusion with a significant increase in glucose utilization and no changes in glucose oxidation, suggesting that alterations in mitochondrial oxidative events are involved in the phenomenon of desensitization.

Glucose Utilization in Rat Hippocampus after Long-Term Recovery from Ischemia

The influence on hippocampal glucose utilization of a transient 10-min forebrain ischemia was quantified in male Wistar rats after 2 and 3 weeks as well as after 3 months by application of the [14C]2-deoxyglucose technique. Ischemia was induced by occlusion of the carotid arteries and simultaneous lowering of the blood pressure to 40 mm Hg. For identification of the hippocampal architecture, sections were stained for perikarya (cresyl violet) and for acetylcholinesterase. The hippocampal regions clearly showed different responses to the ischemic insult. The necrotic pyramidal cells being almost completely removed, significant increases in glucose utilization occurred in most layers of the CA1 sector at 2 and 3 weeks post ischemia, while widespread reductions prevailed in all other sectors and the dentate gyrus. At 3 months after the ischemic insult, glucose utilization was reduced in all hippocampal structures including the CA1 region. The increases in glucose utilization in the CA1 sector are suggested to indicate long-lasting presynaptic hyperexcitation, while the widespread reductions in glucose utilization demonstrate that neuronal activity is also altered in hippocampal areas that do not show major histological damage.

Effects of caffeine and doxapram perfusion on local cerebral glucose utilization in conscious rats

The quantitative autoradiographic 2-[ 14C]deoxyglucose method was used to measure the effects of a continuous infusion of the respiratory stimulants, caffeine or doxapram, 18 mg/kg per h, on local cerebral glucose utilization in the adult male rat. Local cerebral glucose utilization was measured in 54 cerebral structures from different systems. Caffeine induced widespread increases in energy metabolism, resulting in a significant increase in glucose utilization in 25 structures out of the 54 studied. These increases were distributed within all systems studied, sensory, extrapyramidal motor, limbic and hypothalamic systems. In addition, caffeine induced a non-significant, 10–15%, increase in local cerebral glucose utilization in central respiratory areas. Doxapram infusion did not change the rates of glucose utilization in any of the structures. The rates of local cerebral glucose utilization were significantly lower after doxapram than after caffeine exposure in five cerebral areas, among which were three central respiratory ares. The results confirm the absence of side-effects of doxapram as compared to caffeine when used as respiratory stimulant, especially in neonates. These results also favor a preferentially central action of caffeine on respiratory areas and a more peripheral action of doxapram on chemoreceptors, at least at therapeutic levels.

Metabolic mapping of functional activity in rat brain and pituitary after water deprivation.

Glucose utilization in rat brain and pituitary was measured in control and water-deprived rats by autoradiographic assessment of the metabolic trapping of radioactivity from [1-14C]glucose. Two days of water deprivation resulted in significant increases in hematocrit, plasma osmolality and vasopressin levels, indicating a functional activation of magnocellular vasopressin neurons. The uptake and retention of radioactivity from [1-14C]glucose in the dehydrated rats, compared to controls, was 103% greater in the magnocellular portion of the paraventricular nucleus and 74% greater in the supraoptic nucleus. Water deprivation also resulted in significant increases in glucose utilization (30-40%) in the lateral and anterior hypothalamic areas, somatosensory cortex and cingulate cortex. No change in glucose utilization after 2 days of water deprivation was apparent in the parvocellular paraventricular nucleus, periventricular nucleus of the hypothalamus, corpus callosum, organum vasculosum of the lamina terminalis (OVLT) or the subfornical organ (SFO). In the pituitary, glucose utilization was increased in the neural lobe but was unchanged in the anterior and intermediate lobes after water deprivation. Under the conditions of the present study, no increase in metabolic activity was apparent in 2 brain regions thought to be possible sources of osmoreception, the OVLT and SFO. These results do not support, but do not exclude, functional involvement of the OVLT and SFO in regulating the activity of magnocellular neurons of the paraventricular nucleus and supraoptic nucleus during chronic water deprivation.

Glucose utilization in the temporal cortex of affectively ill patients: Positron emission tomography

As temporal lobe dysfunction has been postulated in the affective disorders, the authors investigated glucose utilization in the temporal lobes of 13 affectively ill patients in comparison with 18 normal volunteer controls and 17 previously reported schizophrenic patients, following injections of fluorine 18-2-deoxy- d-glucose (FDG) during somatosensory stimulation to the right forearm. Using a boundary-finding algorithm to outline each temporal lobe, maximum glucose use relative to maximums elsewhere in the same positron emission tomography (PET) slice were calculated. In a small group of moderately to severely depressed patients, this relative measure was significantly reduced in the right (with a similar trend in the left) temporal lobe compared to normal volunteers and the other comparison groups. The lack of a significant increase in glucose utilization, measured either as a maximum or in relation to other areas in the PET scan slice, suggests that a temporal lobe activation or a seizure-like process is not generally occurring during active depressive phases of the illness.

In Vitro Studies of Glucose Metabolism of the Rabbit Urinary Bladder

The urinary bladder, as do all smooth muscle organs, depends on the delivery of oxygen and metabolic substrates for proper functioning. Although glucose metabolism has been studied and evaluated for a variety of smooth muscle systems, little is known about carbohydrate metabolism of the urinary bladder.In the present investigation glucose metabolism and glycogen formation of the urinary bladder of the rabbit was studied in vitro. Isolated urinary bladder strips were prepared from bladder base and body and the following metabolic determinations were made: glucose utilization, glycogen formation, CO2, and lactic acid formation. In addition, the effect of insulin on glucose metabolism was investigated.Glucose utilization was similar in bladder base and body (6.57 ± 0.67μmols/gm./2 hours in combined tissues). Eighty-one percent of the glucose utilized was metabolized to lactate whereas 11% was oxidized to CO2 and 4.7% was incorporated into glycogen. Insulin caused a small but significant increase in glucose utilization by bladder strips.

Metabolic mapping of a cardiac reflex mediated by sympathetic ganglia in dogs

The hypothesis tested was that some cardiac reflexes can be mediated by the neural mechanisms in thoracic sympathetic ganglia in addition to those existing in the spinal cord or brain stem. In mongrel dogs anesthetized with pentobarbital sodium the left stellate (SG) and middle cervical (MCG) ganglion were decentralized, and the left thoracic vagosympathetic trunk was cut cranial to the MCG and caudal to the MCG but above the heart. The left thoracic vagosympathetic trunk below the MCG was then stimulated afferently. A single bolus of 2-[14C]deoxyglucose was injected intravenously and the stimuli repeated periodically toward the decentralized ganglia for 45 min. The heart and ganglia were then removed, frozen, and sectioned for autoradiography. Significant increases in glucose utilization were found in both the SG and MCG compared with ganglia from nonstimulated control animals. Significant increases in the glucose utilization of the endocardial third of the left ventricle were also observed in the reflexly stimulated hearts. Neural mechanisms in the acutely decentralized SG and MCG could modify cardiac glucose utilization within specific areas of the heart. In addition, such ganglionic mechanisms may be concentrated within the caudal half of the SG. These data suggest that many neurons in the thoracic autonomic ganglia may be involved in local cardiac reflexes.

Correlation of dose-dependent effects of acute amphetamine administration on behavior and local cerebral metabolism in rats

Rates of local cerebral glucose utilization were measured by means of the quantitative autoradiographic 2-[ 14C]deoxyglucose technique in conscious rats following the acute administration of d-amphetamine (0.2–5.0 mg/kg, i.v.). Changes in locomotor and stereotypic behavior in similarly treated rats were examined as well. Administration of low doses (0.2 and 0.5 mg/kg) of amphetamine resulted in increased locomotor activity, accompanied by elevations in glucose utilization limited mainly to the nucleus accumbens. A moderate dose of d-amphetamine (1.0 mg/kg) produced locomotion and stereotypic sniffing. Metabolic activity at this dose was increased in the nucleus accumbens, throughout neocortical areas, and in components of the extrapyramidal system. A high dose of amphetamine (5.0 mg/kg) produced stereotypic gnawing and licking and was associated with significant increases in glucose utilization in the extrapyramidal system, most prominently in the subthalamic nucleus. These data demonstrate that the acute administration of d-amphetamine produces effects on local cerebral glucose utilization and on behavior that differ with dose. The results also show a strong coupling between locomotion and the level of metabolic activity in the nucleus accumbens and demonstrate that the different forms of stereotypic behavior elicited by high and moderate doses of amphetamine are correlated with distinct patterns of distribution of local cerebral glucose utilization, indicating mediation by different neuronal circuits.

Regional cerebral glucose utilization rates in rats during asymptomatic period of exposure to 1, 2 and 3 atmospheres absolute of oxygen

A previous study has shown an increase in regional cerebral metabolic rate for glucose prior to the onset of central nervous system oxygen toxicity in rats exposed to 5 atmospheres absolute of oxygen. The present study was designed to measure regional cerebral glucose utilization rates at pressures used for oxygen therapy and prolonged exposures during which rats are known to be asymptomatic. The regional metabolic rate for glucose in 26 brain structures and in gray and white matter of the thoracic and lumbar spinal cord was autoradiographically measured in awake unrestrained rats using the autoradiographic [ 14C]2-deoxyglucose technique. Femoral artery and vein cannulae were inserted 3 days before the experiment. Rats were divided into.four groups of 15: (a) air control; (b) 6 h at 1 atmosphere absolute oxygen; (c) 4 h at 2 atmospheres oxygen; and (d) 2 h at 3 atmospheres oxygen. Statistically significant increases in glucose utilization ( p < 0.05) are seen only in lateral thalamus at 3 atmospheres oxygen, in superior olivary nucleus and inferior colliculus at 2 atmospheres oxygen and in superior olivary nucleus at 1 atmosphere oxygen. The combination of our previous data at 5 atmospheres oxygen and the present results at prolonged and safe exposures to lower pressures indicated that increased glucose utilization in some neuronal structures precedes the onset of the central nervous system manifestations of oxygen toxicity