Rates Of Local Glucose Utilization Research Articles

Biochemical, Metabolic, and Behavioral Characteristics of Immature Chronic Hyperphenylalanemic Rats.

Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of phenylalanine arising from defects in steps to convert phenylalanine to tyrosine. Phe accumulation causes severe mental retardation that can be prevented by timely identification of affected individuals and their placement on a Phe-restricted diet. In spite of many studies in patients and animal models, the basis for acquisition of mental retardation during the critical period of brain development is not adequately understood. All animal models for human disease have advantages and limitations, and characteristics common to different models are most likely to correspond to the disorder. This study established similar levels of Phe exposure in developing rats between 3 and 16 days of age using three models to produce chronic hyperphenylalanemia, and identified changes in brain amino acid levels common to all models that persist for ~16 h of each day. In a representative model, local rates of glucose utilization (CMRglc) were determined at 25-27 days of age, and only selective changes that appeared to depend on Phe exposure were observed. CMRglc was reduced in frontal cortex and thalamus and increased in hippocampus and globus pallidus. Behavioral testing to evaluate neuromuscular competence revealed poor performance in chronically-hyperphenylalanemic rats that persisted for at least 3 weeks after cessation of Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus, the abnormal amino acid environment, including hyperglycinemia, in developing rat brain is associated with selective regional changes in glucose utilization and behavioral abnormalities that are not readily reversed after they are acquired.

Determination of Glucose Utilization Rates in Cultured Astrocytes and Neurons with [14C]deoxyglucose: Progress, Pitfalls, and Discovery of Intracellular Glucose Compartmentation.

2-Deoxy-D-[14C]glucose ([14C]DG) is commonly used to determine local glucose utilization rates (CMRglc) in living brain and to estimate CMRglc in cultured brain cells as rates of [14C]DG phosphorylation. Phosphorylation rates of [14C]DG and its metabolizable fluorescent analog, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), however, do not take into account differences in the kinetics of transport and metabolism of [14C]DG or 2-NBDG and glucose in neuronal and astrocytic cells in cultures or in single cells in brain tissue, and conclusions drawn from these data may, therefore, not be correct. As a first step toward the goal of quantitative determination of CMRglc in astrocytes and neurons in cultures, the steady-state intracellular-to-extracellular concentration ratios (distribution spaces) for glucose and [14C]DG were determined in cultured striatal neurons and astrocytes as functions of extracellular glucose concentration. Unexpectedly, the glucose distribution spaces rose during extreme hypoglycemia, exceeding 1.0 in astrocytes, whereas the [14C]DG distribution space fell at the lowest glucose levels. Calculated CMRglc was greatly overestimated in hypoglycemic and normoglycemic cells because the intracellular glucose concentrations were too high. Determination of the distribution space for [14C]glucose revealed compartmentation of intracellular glucose in astrocytes, and probably, also in neurons. A smaller metabolic pool is readily accessible to hexokinase and communicates with extracellular glucose, whereas the larger pool is sequestered from hexokinase activity. A new experimental approach using double-labeled assays with DG and glucose is suggested to avoid the limitations imposed by glucose compartmentation on metabolic assays.

A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover

Glycogen is degraded during brain activation but its role and contribution to functional energetics in normal activated brain have not been established. In the present study, glycogen utilization in brain of normal conscious rats during sensory stimulation was assessed by three approaches, change in concentration, release of (14)C from pre-labeled glycogen and compensatory increase in utilization of blood glucose (CMR(glc)) evoked by treatment with a glycogen phosphorylase inhibitor. Glycogen level fell in cortex, (14)C release increased in three structures and inhibitor treatment caused regionally selective compensatory increases in CMR(glc) over and above the activation-induced rise in vehicle-treated rats. The compensatory rise in CMR(glc) was highest in sensory-parietal cortex where it corresponded to about half of the stimulus-induced rise in CMR(glcf) in vehicle-treated rats; this response did not correlate with metabolic rate, stimulus-induced rise in CMR(glc) or sequential station in sensory pathway. Thus, glycogen is an active fuel for specific structures in normal activated brain, not simply an emergency fuel depot and flux-generated pyruvate greatly exceeded net accumulation of lactate or net consumption of glycogen during activation. The metabolic fate of glycogen is unknown, but adding glycogen to the fuel consumed during activation would contribute to a fall in CMR(O2)/CMR(glc) ratio.

Lack of effect of insulin on glucose utilization of the hypothalamus in normotensive and hypertensive rats

Hypertension is frequently associated with insulin resistance and enhanced sympathetic activity supposedly mediated by an effect of the hormone on the hypothalamus. In this study we sought to determine whether insulin modifies the functional activity of the hypothalamus and other brain areas of spontaneously hypertensive (SHR) and normotensive WKY rats. The study was carried out in control and hyperinsulinemic, normoglycemic rats. Insulin plasma levels were increased to 198±10 (WKY) or 220±10 μunits/ml (SHR). Brain functional activity was evaluated by the 2-[14C]deoxyglucose method for measuring local rates of glucose utilization. The results show that insulin has no effect on any of the brain areas examined including the hypothalamus, of both WKY and SHR rats. The two strains of rats have comparable cerebral metabolic rates also under basal conditions.

CNS pattern of metabolic activity during tonic pain: evidence for modulation by beta-endorphin.

CNS correlates of acute prolonged pain, and the effects of partial blockade of the central beta-endorphin system, were investigated by the quantitative 2-deoxyglucose technique in unanaesthetized, freely moving rats. Experiments were performed during the second, tonic phase of the behavioural response to a prolonged chemical noxious stimulus (s.c. injection of dilute formalin into a forepaw), or after minor tissue injury (s.c. saline injection). During formalin-induced pain, local glucose utilization rates in the CNS were bilaterally increased in the grey matter of the cervical spinal cord, in spinal white matter tracts and in several supraspinal structures, including portions of the medullary reticular formation, locus coeruleus, lateral parabrachial region, anterior pretectal nucleus, the medial, lateral and posterior thalamic regions, basal ganglia, and the parietal, cingulate, frontal, insular and orbital cortical areas. Pretreatment with anti-beta-endorphin antibodies, injected i.c.v., led to increased metabolism in the tegmental nuclei, locus coeruleus, hypothalamic and thalamic structures, putamen, nucleus accumbens, diagonal band nuclei and dentate gyrus, and in portions of the parietal, cingulate, insular, frontal and orbital cortex. In formalin-injected rats, pretreated with anti-beta-endorphin, behavioural changes indicative of hyperalgesia (increased licking response) were found, which were paralleled by a significant enhancement of functional activity in the anterior pretectal nucleus and in thalamo-cortical systems. A positive correlation was found between the duration of the licking response and metabolic activity of several forebrain regions. These results provide a map of the CNS pattern of metabolic activity during tonic somatic pain, and demonstrate a modulatory role for beta-endorphin in central networks that process somatosensory inputs.

The cerebral metabolic effects of manipulating glutamatergic systems within the basal forebrain in conscious rats.

N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated manipulations of the cortical cholinergic input arising from the basal forebrain differentially affect cognitive function. We used [14C]-2-deoxyglucose autoradiography in conscious rats to map the effects of excitatory amino acid agonist infusions into the nucleus basalis magnocellularis (NBM) on cerebral functional activity, as reflected by local rates of glucose utilization. Acute stimulation of NBM neurones by local infusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), 15 min before glucose use measurement, resulted in glucose use reductions in nine cortical regions innervated by NBM efferents including prefrontal, frontal, sensorimotor and cingulate cortices. NMDA infusions altered glucose use in two cortical areas. Both AMPA and NMDA markedly increased glucose use in the striatum and globus pallidus, with concomitant perturbations in striato-pallidal projection targets including the substantia nigra, entopeduncular nucleus, subthalamic nucleus and lateral habenular nucleus. In contrast, the GABAA agonist muscimol did not affect glucose use in the NBM or neocortical regions, but induced glucose use increases in several subcortical nuclei including the substantia nigra and entopeduncular nucleus. The delayed effects of excitotoxic lesions were assessed 3 weeks after basal forebrain infusions of AMPA, NMDA, ibotenate or quisqualate. Statistically significant glucose use changes only occurred in the hypothalamus after NMDA, and the NBM after ibotenate infusions, although reduced cortical metabolism was apparent following AMPA-induced lesions of the NBM. Results support a dissociation between the functional sequelae of NMDA and non-NMDA receptor-mediated events in the basal forebrain, and long-term compensatory functional adaptation following cortical denervation.

Plasticity of cerebral metabolic whisker maps in adult mice after whisker follicle removal— II. Modifications in the subcortical somatosensory system

The follicles of whiskers C1–3 were removed from the left side of the snout of adult mice. Adjacent whiskers B1–3 and D1–3 were stimulated while local rates of glucose utilization were measured with the [ 14C]2-deoxyglucose method two, four, eight, 64, 160 and ∼250 days after follicle removal. Local metabolic activity in the trigeminal sensory brainstem and somatosensory thalamus was compared with that of unoperated mice with the same stimulation and of mice with the same lesion that had all whiskers clipped. Actual rates of glucose utilization were measured in brainstem subnuclei caudalis and interpolaris whereas metabolic activation was only assessable by colour-coded imaging in brainstem nucleus principalis and in the thalamic ventrobasal complex. Whisker stimulation activated the somatotopically appropriate loci in brainstem and thalamus. In addition, the territory deprived by follicle removal was metabolically activated in subnuclei caudalis and interpolaris at all time intervals examined. The activation was statistically significant in subnucleus interpolaris at two days, indicating that the metabolic representations of whiskers neighbouring the lesion rapidly expanded into the deprived territory. Nucleus principalis showed a broad metabolic activation at two and four days that was absent at the longer time intervals examined. Instead, at ∼250 days the metabolic representations of the whiskers adjacent to the lesion were enlarged into the deprived territory as in the subnuclei. Since metabolic whisker representation in the ventrobasal complex appeared to have changed in the same fashion, follicle removal apparently resulted in congruent modifications of the whisker map in the three nuclei of termination as well as in the thalamic relay at the longest time interval examined. Since metabolic responsiveness of the deprived barrels in barrel cortex of the same animals increased statistically significantly only several months after follicle removal, the novel neural responses in the brainstem were not effectively transmitted to barrel cortex immediately and the slowly evolving cortical modifications are more likely to be associated with regrowth of the connectivity of primary neuron. 28 By contrast, unmasking of hitherto suppressed inputs may underlie the early expansion of metabolic whisker representation in the brainstem.

Low and moderate doses of ethanol produce distinct patterns of cerebral metabolic changes in rats.

The quantitative autoradiographic 2-[14C]deoxyglucose method was used to measure the effects of the acute administration of ethanol on local rates of glucose utilization in male Sprague-Dawley rats. Rates of glucose utilization were measured 10 min after the intraperitoneal administration of 0.00, 0.25, 0.50, and 1.00 g/kg ethanol. The acute administration of the lowest dose of ethanol (0.25 g/kg) significantly increased rates of cerebral metabolism, as compared with vehicle-treated controls, in structures of the mesocorticolimbic and nigrostriatal dopaminergic systems. Among the affected regions were the nucleus accumbens, medial prefrontal cortex, olfactory tubercle, caudate, ventral tegmental area, and substantia nigra. Acute administration of 0.50 g/kg ethanol resulted in similar trends in increased functional activity; however, significant increases were limited to the somatosensory cortex, posterior nucleus accumbens, and the CA3 region of the hippocampus. In contrast, the administration of 1.00 g/kg ethanol produced widespread decreases in rates of glucose utilization in brain regions involved in processing of sensory and motor information, as well as in portions of the limbic system. These data indicate that the effects of acute ethanol administration on functional activity as reflected by rates of glucose utilization are dose-dependent. These cerebral metabolic effects parallel the dose-dependent effects of ethanol on motor behavior, with stimulatory effects generally observed at lower doses and depressive effects at higher doses. Moreover, each of the doses studied produced alterations in functional activity in a unique subset of structures. This suggests that different neuroanatomical circuits mediate the effects of each dose.

Metabolites of 2-deoxy-[14C]glucose in plasma and brain: influence on rate of glucose utilization determined with deoxyglucose method in rat brain.

The [14C]deoxyglucose ([14C]DG) method depends upon quantitative trapping of metabolites in brain at the site of phosphorylation, and in the usual procedure it is assumed that all the label in plasma is in free DG. Our previous finding of labeled nonacidic derivatives of DG in plasma raised the possibility that some metabolites of DG might not be fully retained in body tissues and therefore cause overestimation of the integrated specific activity of the precursor pool determined from assay of label in plasma and/or underestimation of the true size of the metabolite fraction in brain. In the present study, metabolism of DG in rat tissues by secondary pathways was examined and found to be more extensive than previously recognized. When 14C-labeled compounds in ethanol extracts of either plasma or brain were separated by anion exchange HPLC, eight fractions were obtained. 14C-labeled metabolites in plasma were detected after a 35-min lag and gradually increased in amount with time after an intravenous pulse. In brain, deoxyglucose-6-phosphate was further metabolized, mainly to deoxyglucose-1-phosphate and deoxyglucose-1,6-phosphate. These are acid-labile compounds and accounted for approximately 20% of the 14C in the metabolite pool in brain. The rate constants for net loss of 14C from the metabolite pool between 45 and 180 min after a pulse were similar (0.4-0.5%/min) in vivo and in intact postmortem brain. The rate constant for loss of deoxyglucose-6-phosphate (DG-6-P) in vivo (approximately 0.7%/min) was, however, about twice that for postmortem brain, suggesting that a significant fraction of the DG-6-P lost in vivo is due to its further metabolism by energy-dependent reactions. 14C-labeled metabolites of [14C]DG in plasma and brain do not interfere with determination of local rates of glucose utilization in brain in normal, conscious rats by the autoradiographic method if the prescribed procedures and a 45-min experimental period are used.

The role of the olfactory tubercle in the effects of cocaine, morphine and brain-stimulation reward

Using the quantitative 2-[ 14C]deoxyglucose autoradiographic method, local rates of glucose utilization were measured in rats after the administration of morphine or cocaine in the presence or absence of rewarding brain stimulation to the medial forebrain bundle. In animals that did not receive brain stimulation, cocaine significantly increased glucose utilization in the olfactory tubercle, medial prefrontal cortex and substantia nigra pars reticulata, whereas morphine significantly increased glucose metabolism in the olfactory tubercle only. Stimulation itself increased metabolic rates in a number of sites, such as the olfactory tubercle, nucleus accumbens, medial prefrontal cortex, ventral tegmental area and others. However, in self-stimulating animals both morphine and cocaine caused further increases in activity in the olfactory tubercle. Since the olfactory tubercle was the only structure to cause a significant increase in metabolic rate following each treatment, the results implicate this limbic structure in the rewarding effects of morphine, cocaine and brain-stimulation reward.

Morphine decreases cerebral glucose utilization in limbic and forebrain regions while pain has no effect

Morphine alters affective states in humans and produces reinforcement in humans and animal subjects. Therefore, the present study was designed to determine whether morphine affected the functional activity in brain structures involved in emotion and motivation. Since opioid-induced analgesia largely reflects an influence on the emotional component of pain, the effect of pain on activity in these structures was also studied. Local rates of glucose utilization were measured by the 2-deoxy- D[1- 14C]glucose method in the brains of rats, that received morphine or saline, with or without a painful stimulus. Many rostral, and particularly diencephalic, nuclei showed decreased glucose utilization in morphine-treated rats, although caudal regions were mostly unaffected. There were dose-dependent decreases in glucose utilization with doses between 1 and 10 mg/kg morphine. However, nociceptive stimulation, with either formalin or tail-immersion, produced no significant effect on cerebral glucose utilization. The 2-deoxy- D-[1- 14C]-glucose technique, as used here, may lack adequate sensitivity to delineate areas of the brain mediating nociception in rats.

The distribution of changes in local cerebral energy metabolism associated with brain stimulation reward to the medial forebrain bundle of the rat

Using the quantitative 2-[ 14C]deoxyglucose autoradiographic method, local rates of glucose utilization were measured in rats during brain stimulation reward to the medial forebrain bundle. Metabolic activation was observed both rostral and caudal to the site of stimulation. These sites included the nucleus accumbens, olfactory tubercle, lateral septum, and ventral tegmental area. In many cases, increases in glucose utilization occurred bilaterally. These data suggest the involvement of both ascending and descending systems in brain stimulation reward. Furthermore, despite the unilateral nature of the electrical stimulation, increases in glucose utilization were observed both ipsilateral and contralateral to the site of stimulation.

Localized metabolic responses to optokinetic stimulation in the brain stem nuclei and the cerebellum investigated with the [ 14C]2-deoxyglucose method in rats

The localized metabolic effects of monocular optokinetic stimulation to the cerebellar flocculus and brain stem nuclei were measured in pigmented rats. Quantitative [ 14C]2-deoxyglucose autoradiography was performed on alert rats stimulated with a drum either rotated horizontally in the temporonasal direction (optokinetic group) or kept stationary (control group). The superior colliculus in both groups showed a higher amount of activity on the contralateral side to the stimulated eye than on the ipsilateral side. The dorsal cap of the inferior olive, the nucleus of the optic tract, and the lateral pontine nucleus showed a higher amount of activity on the contralateral side only in the optokinetic group. The nucleus reticularis tegmenti pontis and the ventromedial aspect of the cerebellar paraflocculus showed no lateralized activity in either group. Local glucose utilization rates of both flocculi were significantly enhanced in the optokinetic group. Only in the optokinetic group did the ipsilateral flocculus show a higher local glucose utilization rate than the contralateral flocculus. The most enhanced activity was localized in the middle aspect of the rostrocaudal extent of the ipsilateral flocculus. The activity was greater in the granular layer than in the molecular layer or in the white matter. The pattern of activation in the granular layer was characterized by a patchy appearance in the frontal sections. Serial reconstruction of these sections showed metabolic blobs appearing with intervals of several hundred micrometers.

Effect of apamin on local rates of glucose utilization in the brain and the spinal cord in rats

The effects of apamin on local rates of glucose utilization in the brain and spinal cord were studied employing the quantitative autoradiographic deoxyglucose method. Forty-five to 60 min after administration of apamin the animals lost exploratory behavior, remaining completely immobile, with the 4 limbs overextended, unresponsive to auditory stimuli. Out of 30 neural structures examined, glucose utilization was significantly decreased in the cochlear n., superior olivary n., lateral lemniscus, inferior colliculus, medial geniculate body, fastigial n., globus pallidus, caudate-putamen, n. accumbens and the lumbar ventral horn of the spinal cord. These results show that apamin specifically affects the functional activity of the auditory and motor structures.

Effects of leukocytic pyrogen (interleukin-1) on local cerebral glucose utilization in rats with and without premedication with indomethacin or dexamethasone.

Changes in body temperature were recorded in freely moving rats given phosphate-buffered saline or leukocytic pyrogen (interleukin-1) while the animals were in an infant incubator maintained at 25.5 +/- 0.5 degrees C. The leukocytic pyrogen increased body temperature by at least 1 degree C within 1 h. This rise in temperature was prevented by premedication with indomethacin (10 mg/kg) but not dexamethasone (0.5 mg/kg) given 15 min before the leukocytic pyrogen. Local rates of glucose utilization were measured in 47 regions of the central nervous system. In none of the regions previously reported to have an increased rate of glucose utilization associated with an ambient temperature of 32.5 degrees C (McCulloch et al., 1982b) was an increase found in the present experiments. It was concluded that the intensity of the changes in local cerebral glucose utilization in response to the fever caused by the leukocytic pyrogen was insufficient to be measured. Neither indomethacin nor dexamethasone caused remarkable changes in rates of local glucose utilization.

Metabolic responses of the flocculus to optokinetic stimuli as revealed by the [ 14C]2-deoxyglucose method in pigmented rats

By means of the [ 14C]2-deoxyglucose method, metabolic activity in the flocculus during monocular temporonasal optokinetic stimulation was investigated in alert pigmented rats. Local glucose utilization rates of both flocculi were significantly enhanced in the optokinetically stimulated animals. The flocculus ipsilateral to the stimulated eye showed an enhanced local glucose utilization rate as compared with the contralateral flocculus. The most enhanced activity was localized in the middle part of the rostrocaudal extent of the ipsilateral flocculus, and was characterized by its patchy appearance in the granular layer.

Coma associated with flaccidity produced by fluid-percussion concussion in the cat. II: Contribution of activity in the pontine inhibitory system.

In the preceding paper we reported that concussive levels of fluid-percussion head injury can produce transient flaccidity of postural muscles associated with other indices of coma. This reversible coma associated with flaccidity follows an initial period of generalized areflexia and occurs in the absence of EEG slow waves. The present study investigated the physiological mechanisms underlying the flaccidity following concussive head injury be recording dorsal and ventral root potentials of the spinal cord. Studies indicated that, during the initial period of generalized areflexia, afferent input transmission was depressed although the excitability of motoneuronal pools was increased. In contrast, during periods of flaccidity, spinal cord somatomotor functions were depressed while transmission of afferent inputs was recovering. Systematic transection of the brain stem showed that activity within structures lying between collicular and midpontine levels is necessary to produce this latter condition. Cholinergic activation of pontine inhibitory areas within this same region of the rostral pons can produce profound descending inhibitory influences on postural somatomotor function in conjunction with other features of coma including suppression of eye-opening responses. Such effects occur without EEG slow waves. Moreover, other data indicate that local rates of glucose utilization within this pontine inhibitory area increase following concussive head injury. Thus, it is possible that a predominance of activity within the pontine inhibitory area could provide at least one neural basis for the reversible comatose state following concussive head injury characterized by close association between flaccidity and other indices of coma. Possible relationships of these data to clinically observed features of concussion are discussed.

Effect of moderate level x-radiation to brain on cerebral glucose utilization.

The effect of x-radiation in doses used in treatment of brain malignancies has previously been established largely by histologic examination of the tissue or by observation of a deficit in function. At moderate dose levels such effects are usually delayed and are vascular in origin. We have used the 2-[14C]deoxyglucose method for the quantitative measurement of local cerebral glucose utilization to learn whether x-radiation administered to rat brain in a dose below that which is known to result in any histologic change may nevertheless affect the brain's local rates of glucose utilization. Measurements were made 4 days and 4 weeks after exposure of groups of rats to 1,500 rad. Rates of glucose utilization in 54 gray and eight white matter structures in both groups were compared with rates in sham-irradiated controls. Statistically significantly lower rates were found in 16 structures in rats 4 days after radiation and in 25 structures 4 weeks after radiation exposure. A weighted average rate for the brain as a whole was approximately 15% below that of the controls for both radiated groups, but this difference was short of being of statistical significance. It is clear from this study that the metabolic rates of some brain structures are reduced following moderate doses of x-radiation.

Alternative approach to single-scan estimation of cerebral glucose metabolic rate using glucose analogs, with particular application to ischemia.

In the glucose analog method for determining local glucose utilization rates, time courses of tissue and plasma radioactivity are measured and then analyzed in terms of first-order exchange of label between tissue compartments. The rate of glucose utilization is assumed to have a fixed, linear relationship to the analog phosphorylation rate calculated from the fitted rate constants. Accurate estimation of the rate constants requires many hours of dynamic data acquisition. Therefore, techniques assuming a linear relationship between analog phosphorylation rate and total tissue concentration of label were developed to predict glucose utilization rates from a single scan. Previously reported linearizations differ in their sensitivity to differences between current and average kinetic rate constants, and thus in their accuracy. We have developed a method that is insensitive to the presumed value of the blood flow-capillary wall transport parameter k1. This new single-scan approach has been validated by comparison of the single-scan metabolic rate values with the values calculated from the dynamic measurements.

Extrastriatal circuits activated by intrastriatal muscimol: A[ 14C]2-deoxyglucose investigation

The quantitative autoradiographic [ 14C]2-deoxyglucose technique has been employed in conscious, lightly restrained rats to investigate the functional consequences (which are reflected as alterations in local rates of glucose utilization) of unilateral intrastriatal administration of the GABAergic agonist, muscimol. Intrastriatal injections of muscimol (500 ng) effect a widespread, homogeneous reduction (by 33%) in glucose utilization throughout the ipsilateral striatum. Increased glucose utilization following intrastriatal muscimol injection was observed in each region to which the principal striatal efferent projections are directed (ipsilateral globus pallidus increased by 29%; ipsilateral entopeduncular nucleus increased by 33%; ipsilateral pars reticulata increased by 46%). Significant focal alterations in glucose utilization occurred in a number of other regions ipsilateral to the injection, including lateral habenular nucleus (increased by 16%), pars compacta of the substantia nigra (increased by 28%), ventrolateral nucleus of the thalamus (decreased by 40%), sensory-motor cortex (decreased by 47%), deep layer of the superior colliculus (decreased by 18%), and subthalamic nucleus (decreased by 18%). In the overwhelming majority of brain regions examined, glucose utilization was unaltered by intrastriatal administration of muscimol. All regions which displayed significant alterations in glucose use with intrastriatal muscimol are known to have direct connections with the striatum (e.g. pallidus and nigra), or to be anatomical components in polysynaptic striatal outflow pathways (e.g. striatal-pallidal-ventral thalamic-neocortical circuit). The present results indicate that activity within striatal efferent circuits can be differentially modified by the effects of the GABAergic agonist, muscimol, within the caudate nucleus.