2-deoxyglucose Technique Research Articles

Acute Ethanol Effects on Local Cerebral Glucose Utilization in Select Central Nervous System Regions of Adolescent Alcohol‐Preferring (P) and Alcohol‐Nonpreferring (NP) Rats

Alcohol abuse among adolescents is a major health and developmental problem. The 2-[(14)C]deoxyglucose (2-DG) technique allows for the in vivo quantification of local cerebral glucose utilization (LCGU) as a measure of functional neuronal activity. Local cerebral glucose utilization rates were examined after acute ethanol administration within selected brain regions of adolescent alcohol-preferring (P) and -nonpreferring (NP) rats. Postnatal day 45 male P and NP rats were injected with saline or 1.0 g/kg ethanol, i.p., 10 minutes prior to an intravenous bolus of [(14)C]-2-deoxyglucose (125 microCi/kg). Image densities were determined using quantitative autoradiography and LCGU values calculated. Acute ethanol injection significantly decreased LCGU rates in select brain regions including the olfactory tubercles, the frontal cortex (Fr), and subregions of the posterior hippocampus (pCA1 and pCA3). Acute ethanol had no significant effects on LCGU rates in any region of the adolescent NP rats. Significant basal LCGU rate differences were apparent between the rat lines in a nearly global fashion with adolescent P rats having much higher basal LCGU rates compared with adolescent NP rats. These findings suggest that the adolescent P and NP rats are less sensitive to the effects of acute ethanol than their adult counterparts. The adolescent P rat is relatively more sensitive to the initial effects of acute ethanol in select brain regions as compared with the adolescent NP rat. Additionally, the innate hyper-excited state of the adolescent P central nervous system is a likely factor in the development of their high alcohol drinking behaviors.

Modifications of local cerebral glucose utilization during circadian food-anticipatory activity

Food-anticipatory activity that animals express before a daily timed meal is considered as the behavioral output of a feeding-entrainable oscillator whose functional neuroanatomy is still unknown. In order to identify the possible brain areas involved in that timing mechanism, we investigated local cerebral metabolic rate for glucose during food-anticipatory activity produced either by a 4-h daily access to food starting 4 h after light onset or by a hypocaloric feeding provided at the same time. Local cerebral metabolic rate for glucose measured by the labeled 2-[ 14C]-deoxyglucose technique was quantified in 40 structures. In both groups of food-restricted rats, three brain regions (the nucleus of the solitary tract, the cerebellar cortex and the medial preoptic area) showed a decrease in local cerebral metabolic rate for glucose, compared with control ad libitum animals. In addition, only one structure, the paraventricular thalamic nucleus, was affected by temporal restricted feeding, and not by hypocaloric feeding, compared with ad libitum rats. By contrast, three brain regions, i.e. the intergeniculate leaflets, the paraventricular hypothalamic and the arcuate nuclei, showed specifically metabolic decreases during anticipation of hypocaloric feeding, and not during anticipation of temporal restricted feeding, compared with the ad libitum group. Expression of food-anticipatory activity appears to be regulated by an integrated neural circuit of brainstem and hypothalamic pathways, with hypocaloric feeding involving more extensive forebrain areas than temporal restricted feeding.

The organization of orientation selectivity throughout macaque visual cortex.

A double-label deoxyglucose technique was used to study orientation columns throughout visual cortex in awake behaving macaques. Four macaques were trained to fixate while contrastreversing, stationary gratings or one-dimensional noise of a single orientation or an orthogonal orientation were presented, during uptake of [14C]deoxyglucose ([14C]DG) or [3H]DG, respectively. The two orthogonal stimulus orientations produced DG-labeled columns that were maximally separated in the two isotope maps (inter-digitated) in four areas: V1, V2, V3 and VP. The topographic change from interdigitated to overlapping columns occurred abruptly rather than gradually, at corresponding cortical area borders (e.g. VP and V4v, respectively). In addition, the data suggest that orientation column topography systematically changes with retinotopic eccentricity. In V1, the orientation columns systematically avoided the cytochrome oxidase blobs in the parafoveal representation, but converged closer to the blobs in the foveal representation. A control experiment indicated that this was unlikely to reflect eccentricity-dependent differences in cortical spatial frequency sensitivity. A similar eccentricity-dependent change in the topography of orientation columns occurred in V2. In parafoveal but not foveal visual field representations of V2, the orientation columns were centered on the thick cytochrome oxidase stripes, extended into the adjacent interstripe region, but were virtually absent in the thin stripes.

Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidation.

The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Immunoblot analysis with antibodies raised against recombinant PDK isoforms demonstrated changes in PDK isoform expression in response to experimental hyperthyroidism (100 microg/100 g body weight; 3 days) that was selective for fast-twitch vs slow-twitch skeletal muscle in that PDK2 expression was increased in the fast-twitch skeletal muscle (the anterior tibialis) (by 1. 6-fold; P<0.05) but not in the slow-twitch muscle (the soleus). PDK4 protein expression was increased by experimental hyperthyroidism in both muscle types, there being a greater response in the anterior tibialis (4.2-fold increase; P<0.05) than in the soleus (3.2-fold increase; P<0.05). The hyperthyroidism-associated up-regulation of PDK4 expression was observed in conjunction with suppression of skeletal-muscle PDC activity, but not suppression of glucose uptake/phosphorylation, as measured in vivo in conscious unrestrained rats (using the 2-[(3)H]deoxyglucose technique). We propose that increased PDK isoform expression contributes to the pathology of hyperthyroidism and to PDC inactivation by facilitating the operation of the glucose --> lactate --> glucose (Cori) and glucose --> alanine --> glucose cycles. We also propose that enhanced relative expression of the pyruvate-insensitive PDK isoform (PDK4) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation, sparing pyruvate for non-oxidative entry into the tricarboxylic acid (TCA) cycle, and thereby supporting entry of acetyl-CoA (derived from fatty acid oxidation) into the TCA cycle.

Effects of acute and chronic treatment with fluoxetine on regional glucose cerebral metabolism in rats: implications for clinical therapies

The wide therapeutic spectrum of fluoxetine (e.g., antidepressant, antipanic, antiphobic, antiobsessive, analgesic, antimigraine) requires long-term administration and adaptive changes. To test whether adaptation involves the serotonin (5-HT) transporters, we measured the effects of fluoxetine on the regional cerebral metabolic rate for glucose (rCMRglc) in control rats or in rats pretreated for 2 weeks with fluoxetine (8 mg/kg, i.p., daily, 2 days wash out); rCMRglc was measured in 56 brain regions, using the quantitative [ 14 C ]deoxyglucose technique, at 30 min after i.p. administration of fluoxetine 0.4, 4 or 40 mg/kg, i.p., to non-pretreated rats or fluoxetine 4 mg/kg to pretreated rats. In non-pretreated rats, fluoxetine reduced rCMRglc in a dose-dependent fashion in 4 (7%, mean decrease 11%), 28 (50%, mean decrease 23%) and 37 (66%, mean decrease 32%) brain regions. In chronic fluoxetine-pretreated rats, fluoxetine decreased rCMRglc to a substantially lesser degree (eight regions, 14%; mean decrease, 10%). Subcortical brain regions (i.e., hypothalamic paraventricular, locus coeruleus and basal ganglia nuclei) that mediate the physiological responses to stress were very sensitive to fluoxetine acutely and subsensitive after chronic treatment. As kinetic tolerance to fluoxetine does not occur during chronic administration, the diminished rCMRglc responsivity to fluoxetine reflects dynamic, adaptive tolerance of 5-HT transporters and, consequently, increased synaptic 5-HT concentrations; the findings suggest that fluoxetine may be therapeutic by increasing the 5-HT-negative modulation upon areas that drive the abnormally hyperactive responses to stress found in several neuropsychiatric conditions.

Supraspinal metabolic activity changes in the rat during adjuvant monoarthritis

Pain is a multi-dimensional experience including sensory-discriminative and affective-motivational components. The attribution of such components to a corresponding cerebral neuronal substrate in the brain refers to conclusions drawn from electrical brain stimulation, lesion studies, topographic mappings and metabolic imaging. Increases in neuronal metabolic activity in supraspinal brain regions, suggested to be involved in the central processing of pain, have previously been shown in various animal studies. The present investigation is the first to describe supraspinal structures which show increased metabolic activity during ongoing monoarthritic pain at multiple time-points. Experimental chronic monoarthritis of a hindlimb induced by complete Freund's adjuvant is one of the most used models in studies of neuronal plasticity associated with chronic pain. Such animals show typical symptoms of hyperalgesia and allodynia for a prolonged period. Metabolic activity changes in supraspinal brain regions during monoarthritis were assessed using the quantitative [ 14C]-2deoxyglucose technique at two, four, 14 days of the disease and, furthermore, in a group of 14-day monoarthritic rats which were mechanically stimulated by repeated extensions of the inflamed joint. Local glucose utilization was determined ipsi- and contralateral to the arthritic hindpaw in more than 50 brain regions at various supraspinal levels, and compared with saline-injected controls. At two and 14 days of monoarthritis significant bilateral increases in glucose utilization were seen in many brain structures, including brainstem, thalamic, limbic and cortical regions. Within the brainstem, animals with 14-day monoarthritis showed a higher number of regions with increased metabolic activity compared with two days. No differences between ipsi- and contralateral sides were detected in any of the experimental groups. Average increases ranged from 20 to 40% compared with controls and maximum values were detected in specific brain regions, such as the anterior pretectal nucleus, the anterior cingulate cortex and the nucleus accumbens. Interestingly, at four days of monoarthritis, the glucose utilization values were in the control range in almost all regions studied. Moreover, in monoarthritic rats receiving an additional noxious mechanical stimulation, the rates of glucose utilization were also comparable to controls in all brain areas investigated. Such patterns of brain metabolic activity agreed with concomitant changes in the lumbar spinal cord, described in the accompanying report. 112 The present data show that a large array of supraspinal structures displays elevated metabolic activity during painful monoarthritis, with a non-linear profile for the time-points investigated. This observation most probably reflects mechanisms of transmission and modulation of nociceptive input arising from the monoarthritis and accompanying its development.

Comparison of Frequency‐specific c‐Fos Expression and Fluoro‐2‐deoxyglucose Uptake in Auditory Cortex of Gerbils (Meriones unguiculatus)

Induction of c-Fos in the auditory cortex of gerbils was investigated immunocytochemically 1 h after single, triple or 1 h continuous stimulation with a series of narrow band frequency-modulated tone bursts. With single stimulation c-Fos immunoreactive neurons were chiefly found in the primary auditory field (AI), where they formed a narrow frequency-specific column across layers II-VI. Side-band-like patterns adjacent to this column appeared characteristically with triple stimulation. Immunoreactive cell density in the anterior auditory field and the caudal fields was sparse and location not frequency specific with single or triple stimulation. Spatial comparisons of c-Fos immunoreactive neuron density with 2-deoxy-2-fluoro-D-glucose (FDG) autoradiography in the same animals after 1 h of stimulation revealed spreading of c-Fos expression in neurons across the tonotopic maps of the AI and in the rostral and caudal fields of the auditory cortex. The pattern of the highest density of c-Fos labelled cells in the AI still matched the peak labelling of FDG autoradiographs. The results show that the postsynaptic marker c-Fos reflects the frequency representation in the AI with single or triple stimulation yet with a higher spatial resolution than the deoxyglucose technique. Longer stimulation causes nontonotopic intracortical spreading of the c-Fos-inducing message, a phenomenon potentially reflecting the effects of cooperativity in the maps.

FR139317, a specific ET A-receptor antagonist, inhibits cerebral activation by intraventricular endothelin-1 in conscious rats

A comprehensive series of time-related behavioral, physiological and cerebral metabolic studies was conducted using conscious Sprague-Dawley rats to discern the anti-endothelin (ET) properties of the specific ETA receptor antagonist, FR139317. Endothelin-1 (9 pmol given by injection into one lateral ventricle, i.c.v.) produced convulsions, acute arterial hypertension, arterial hyperglycemia, and hyperventilation. Brain structures close to the i.c.v. site of injection, such as the caudate nucleus, lateral septal nucleus, corpus callosum and hippocampal CA3 medial lamellae, as well as 14 other individual structures, displayed moderate-to-intense levels of metabolic activation after endothelin. Data were assessed quantitatively by means of the autoradiographic [14C]deoxyglucose technique combined with image analysis. Neural circuits in the efferent projection paths of the stimulated forebrain structures, such as the midbrain oculomotor complex, amygdaloid nuclei, substantia nigra pars reticulata and caudal subicular subregions of the hippocampal formation, were stimulated focally by endothelin. Specific medullary nuclei and cerebellar cortical subregions displayed high rates of glucose metabolism following endothelin injection at the time of maximum behavioral and physiological stimulation. I.c.v. treatment with > or = 14 nmol FR139317 before endothelin significantly inhibited the effects produced by the peptide. At the highest dose of FR139317 (28 nmol), there was only mild behavioral stimulation following endothelin injection, and hypermetabolic responses in the brain were abolished except in two specific areas of the cerebellar cortex (approx 40% increases in metabolic activity in the copula pyramis and paramedian lobule). The results indicate that the cerebral stimulatory effects of i.c.v. endothelin are mediated by the A type of endothelin receptor. By itself, i.c.v. FR139317 had no effects on the parameters assessed. Further evaluation of FR139317 is warranted as a possible therapeutic agent for neuropathologies suspected of deriving from central neural or vascular stimulation by endothelin, such as aneurysmal vasospasm, ischemia, excitotoxicity, and peptide-mediated epilepsies.

NMDA-mediated metabolic activation of the cerebellar cortex in behaving rats by the neuropeptide endothelin-1

Generalized barrel-rolling convulsions and focal hypermetabolic responses in the cerebellar cortex of conscious rats to lateral ventricular injection of the neuropeptide, endothelin-1 (ET; 9 pmol), were diminished or eliminated by i.c.v. pretreatment with the glutamatergic NMDA receptor antagonist, MK-801 (44 nmol). Using the quantitative autoradiographic [ 14C]deoxyglucose technique, we assessed rates of glucose metabolism in individual structures anatomically connecting forebrain nuclei within a polysynaptic network linked to the cerebellar cortex. Cerebellar cortical afferent sources from specific subnuclei of the inferior olivary complex, cuneate nucleus, and medial vestibular nucleus, all of which were hypermetabolic following injection of ET alone, were also inhibited by MK-801. The findings indicate that a convulsive i.c.v. dose of ET elicits an NMDA-related stimulatory effect, whose origin is probably at the periventricular caudate nucleus, that activates rates of glucose metabolism in several afferent sources and subregions of the cerebellar cortex involved in the regulation of equilibrium, posture, and the visuovestibular system.

Tetrahydroaminoacridine and Physostigmine Increase Cerebral Glucose Utilization in Specific Cortical and Subcortical Regions in the Rat

The effects of the anticholinesterases tetrahydroaminoacridine (THA) and physostigmine on local cerebral glucose utilization (LCGU) were studied in the conscious rat, using the autoradiographic [14C]deoxyglucose technique. THA (5 mg/kg i.p.) increased LCGU significantly in 8 of the 43 regions studied. A higher dose of THA (10 mg/kg) produced a metabolic activation in 19 of the 43 regions. LCGU increased in cortical areas (including parietal and temporal cortices), the septohippocampal system, the thalamus, the lateral habenula, the basolateral amygdala, the superior colliculus, and the substantia nigra. Scopolamine (4 mg/kg i.p.) reversed the THA-induced LCGU increase. Physostigmine (0.2 and 0.5 mg/kg) increased LCGU in 15 and 22 regions, respectively. The average magnitude of the change induced by 0.5 mg/kg of physostigmine was similar to that observed after THA at 10 mg/kg, but the topography of the effects was somewhat different. Physostigmine increased LCGU in the preoptic magnocellular area, the brainstem, and the cerebellum but not in the parietal cortex. The effects in the septohippocampal system were smaller than those induced by THA. The regional topography of the LCGU increase overlapped the distribution of the M2 muscarinic receptors and that of acetylcholinesterase activity. These data suggest that the major effects of THA and physostigmine on LCGU result from their anticholinesterase action.

Calcium-mediated metabolic stimulation of neuroendocrine structures by intraventricular endothelin-1 in conscious rats

We examined the hypothesis that the vascular- and brain-derived peptide, endothelin-1 (ET), would affect cerebral neuroendocrine structures when administered via the peripheral circulation or via a lateral cerebral ventricle (i.c.v.). ET was infused intravenously (14 nmol/min) or injected i.c.v. (9 pmol) in conscious rats in which local cerebral glucose metabolism was assessed by the quantitative autoradiographic [ 14C]deoxyglucose technique. Whereas intravenously infused ET was previously demonstrated to selectively stimulate metabolic activity in the pituitary intermediate and anterior lobes of conscious rats, it was without effect in 20 individual structures or subnuclei involved in neuroendocrine functions, including several circumventricular organs. Intraventricular ET, however, caused hypermetabolic responses in 9 neuroendocrine structures, including the pineal gland, subfornical organ, median eminence, the hypothalamic paraventricular and supraoptic nuclei, and other hypothalamic and preoptic structures. The metabolic stimulation resulting from central ET was abolished or attenuated regionally by i.c.v. pretreatment with the calcium L-channel inhibitor, nimodipine. The findings indicate that i.c.v. ET elicits a calcium-mediated hypermetabolic effect on several neuroendocrine structures in the forebrain involved in the regulation of fluid homeostasis, the cardiovascular system, and body temperature.

Potent Metabolic Stimulation of Septal Gray and Cerebral White Matter in Vivo by Intraventricular Endothelin and Nitric Oxide

Endothelin-1 (ET) and sodium nitroprusside (SNP, which liberates nitric oxide, NO) were given alone or together into a lateral cerebral ventricle (icv) of anesthetized rats to assess their potential interaction on cerebral rates of glucose metabolism (autoradiographic [ 14C]deoxyglucose technique). ET (9 pmol) produced hypermetabolic effects ipsilaterally in the septal nuclei and periventricular white matter. NO lesioned the septum, which displayed neuronal damage and diminished metabolic activity, and evoked potent increases in glucose metabolism bilaterally in commissural and projection white matter tracts. Together, ET and NO had synergistic hypermetabolic effects in the hippocampal fimbria, but were antagonistic on the metabolic rate of the lateral septal nucleus and choroid plexus. The results reveal an extraordinary sensitivity in the metabolic rate of septal gray matter to ET and of white matter fibers to NO in vivo. Icv administration offers a useful approach for examination of the metabolic and toxicological properties of the novel neurotransmitter substances ET and NO on septal neurons, myelinated fibers, and choroidal epithelia.

Time- and dose-dependent effects of the serotonergic agent quipazine on regional cerebral metabolism in rats

The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male adult Fischer-344 rats after administration of quipazine, a serotonin 5-HT 2–3 receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [ 14C]deoxyglucose technique, in 92 brain regions at 30, 60, 90 and 120 min after quipazine 20 mg/kg i.p. and at 60 min after quipazine 5 mg/kg i.p. Peak metabolic effects were observed 60 min after quipazine 20 mg/kg i.p. when rCMRglc was significantly elevated in 27 (29%) brain regions (mean rise 17%). Quipazine increased rCMRglc in brain regions with high densities of 5-HT 3 receptors (area postrema, olfactory tubercle, amygdala), in dopaminergic nuclei (substantia nigra pars compacta and pars reticulata) and terminal fields of their projections (zona incerta, subthalamic nucleus, preoptic magnocellular area, nucleus of facial nerve). The topographic distribution and direction of rCMRglc changes induced by quizapine are different from those produced by the 5-HT 2 agonist 1-(2,5-dimethoxy-4-iodophenyl-4-iodophenyl)-2-aminopropane and, consistent with the pharmacological and binding properties of quipazine, suggest a preferential activation of 5-HT 3 receptors.

A new experimental model of epilepsy based on the intraventricular injection of endothelin.

Injection of endothelin-1 (ET-1, 9 pmol) into a lateral cerebral ventricle (LCV) of rats produces barrel-rolling and other convulsive signs that resemble those of generalized seizures in some types of epilepsy. Using the quantitative autoradiographic [14C]deoxyglucose technique, we documented that the neuroanatomical metabolic correlates of the ET-1-induced convulsions in rats are high rates of glucose utilization by structures near the site of LCV injection and throughout a diverse circuit of anatomically related brain regions. We speculate that this circuitry connects the caudate nucleus (putative site of initial stimulation in the forebrain) to the paramedian lobule and vermis of the caudal cerebellar cortex in the hindbrain. We evaluated the behavioral, physiological, and hypermetabolic responses to central ET-1 in the presence of three agents with anticonvulsant properties, providing clues about the cellular mechanisms of this convulsive and hypermetabolic state. Intraventricular MK-801 [a noncompetitive antagonist of glutamic acid N-methyl-D-aspartate (NMDA) receptors], nimodipine (an antagonist of dihydropyridine-sensitive, voltage-gated calcium L-channels), or methylene blue (an inhibitor of guanylate cyclase, the enzyme on which nitric oxide acts) each produced significant attenuation of the behavioral and cerebral metabolic activation. The results introduce several quantitative parameters for an experimental model of employing intraventricular ET-1 in rats to study mechanisms of peptidergic convulsive disorders and the efficacies of promising anticonvulsant compounds in the treatment of epilepsy.

14C]deoxyglucose labelling of functional activity in the cephalopod central nervous system.

For the first time, the [14C]deoxyglucose radioautographic technique has been successfully used to map physiological activity in cephalopod brains. In unilaterally blinded octopus and cuttlefish, the optic lobe of the deprived side showed a decreased uptake of the labelled tracer. This suggests that the uptake is related to functional activity. The potential of the [14C]deoxyglucose technique as a powerful tool in studying the functional organization of cephalopod brains is discussed.

Acute hypoxia induces specific changes in local cerebral glucose utilization at different postnatal ages in the rat

The quantitative autoradiographic 2-[ 14C]-deoxyglucose technique (2-DG) was applied to measure the effects of an acute hypoxic exposure on local cerebral metabolic rates for glucose (LCMRglcs) in the 10 (P10)-, 14 (P14)-, and 21 (P21)-day-old rat. The animals were exposed to hypoxic (7% O 2/93% N 2) or control gas mixture (21% O 2/79% N 2) for 20 min before the initiation and for the duration of the 2-DG procedure. Lumped constants were not affected by hypoxia at any age. At P10, the exposure to the hypoxic gas mixture induced a generalized increase in LCMRglc which affected 41 structures of the 45 studied. At P14, average cerebral glucose utilization was similar in hypoxic and control rats. LCMRglc increased in 5 areas and decreased in 11 regions, mainly brainstem and respiratory areas in hypoxic rats. Finally, at P21, LCMRglc decreased in 11 structures of hypoxic rats. The increase in LCMRglc in the hypoxic 10-day-old rat likely reflects stimulation of anaerobic glycolysis. Conversely, at P14 and P21, when the brain has become more dependent upon oxygen supply for its energy metabolism, levels of LCMRglc are similar in both groups of animals or decreased in a few structures of hypoxic compared to normoxic rats. The results of the present study show that the immature brain responds to an acute hypoxic insult in a specific way according to its maturational state. They are also in good accordance with the higher resistance of the immature animal to oxygen deprivation.

Effect of Ischemia and Reperfusion on λ of the Lumped Constant of the [14C]Deoxyglucose Technique

We measured the parameter lambda, which is the ratio of the distribution spaces of 2-deoxy-D-glucose (DG) and glucose in the brain, in a model of focal cerebral ischemia in the cat. lambda is the parameter in the lumped constant of the [14C]DG technique most susceptible to changes in ischemia. Cats were subjected to occlusion of the middle cerebral artery for a period of 2 h. During the last 60 min of occlusion, [14C]DG was infused in a programmed fashion so as to obtain a stable arterial blood [14C]DG concentration. The brain was funnel-frozen to preserve tissue metabolites and the frozen brain was sampled regionally (4 to 7-mg samples) for local concentrations of glucose, ATP, phosphocreatine (PCr), and lactate. In a separate series of cats, the infusion of [14C]DG was started after 2 h of occlusion and 3 h of recirculation. In both series, lambda declined slightly for increased levels of tissue glucose and increased appreciably as tissue glucose decreased. A similar relationship was observed between lambda and ATP and PCr, although the correlation was not as clear. Since lambda, and hence the lumped constant, increases in ischemia as well as in postischemic tissue, it is important to measure tissue glucose concentration if quantitative values of local cerebral glucose metabolism are desired in this condition.

Studies of central nervous system disorders with single photon emission computed tomography and positron emission tomography: Evolution over the past 2 decades

Single photon emission computed tomography (SPECT) was introduced in the 1960s to detect breakdowns in the blood-brain barrier and was replaced by x-ray computed tomography in the mid-1970s. The development of the deoxyglucose (DG) technique to measure regional cerebral glucose metabolism by employing either autoradiography, using 14CDG, or positron emission tomography (PET), using 18FDG, added a major dimension to the investigation of brain function. In the late 1970s and early 1980s, the FDG-PET technique was widely used to examine a variety of neuropsychiatric disorders. It soon became apparent that functional imaging was more sensitive than anatomic imaging in detecting abnormalities of the brain related to aging, dementia, tumors, seizures, cerebral vascular accidents, and psychiatric problems. Because of its complexity and the cost involved, PET was used in a limited number of centers in the United States. However, the success of PET resulted in the resurgence of interest in SPECT as an alternative technology after almost a decade. This became possible because of the synthesis of iodine 123- and technetium 99m-labeled radiopharmaceuticals to determine regional cerebral blood flow. Since blood flow and metabolism are coupled in most pathological states, patterns of abnormality noted on SPECT were similar to those seen on PET in many disorders. Since the introduction of high resolution SPECT imaging instruments, the role of SPECT has been further enhanced. The successful synthesis of both positron and single emitting radioligands to image dopamine and other receptors has started a new era in neurosciences and will have a far-reaching impact on the day-to-day practice of neuropsychiatry.

The distribution of blood flow and glucose uptake within single skeletal muscles in the awake rabbit

We have previously described a substantial regional heterogeneity both in blood flow and in glucose uptake within single skeletal muscles in anaesthetized rabbits. These heterogeneities could be related to effects of anaesthesia. The main goal of the present study was therefore to study regional muscle blood flow and muscle glucose uptake in awake rabbits. We used the microsphere method and the deoxyglucose technique for assessment of regional blood flow and regional glucose uptake respectively. The measurements were performed in 0.25-g regions from hind leg muscles. Some rabbits were first studied while awake and then during anaesthesia. Others were studied while either awake or anaesthetized. The degree of regional heterogeneity in blood flow and in glucose uptake was similar in awake and anaesthetized rabbits. Both temporal and spatial heterogeneity in blood flow were present. Evidence was found for vasomotion with a cycle time exceeding 45 min in awake rabbits. This perfusion pattern was similar in rabbits in which either the motor or sympathetic vasomotor nerves or both had been blocked. We conclude that regional perfusion and glucose uptake within single muscles are also markedly heterogeneous in awake rabbits. Regional, non-synchronized fluctuations in blood flow with a long cycle time seem to be an important part of this perfusion heterogeneity.

Time courses of behavioral and regional cerebral metabolic responses to different doses of meta-chlorophenylpiperazine in awake rats

The time course and relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) and of motor behavior were measured in awake male adult Fischer-344 rats after administration of meta-chlorophenylpiperazine (MCPP), a serotonin-1B receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [ 14C]deoxyglucose technique, in 71 brain regions at 5, 15, 30 and 60 min after administration of MCPP 2.5 mg/kg i.p., and at 15 min after MCPP 25 and 40 mg/kg. The time course of performance on a rotating rod was measured periodically for 60 min after MCPP 2.5 mg/kg, a dose which impaired locomotion and reduced rCMRglc maximally at 15–30 min after its administration. At 15 min, rCMRglc declined significantly in 28 (40%) of the areas studied (mean decline 16%). Most regions affected were telencephalic or diencephalic, corresponding to the projection areas of serotonergic fibers arising from the raphe nuclei. After higher doses of MCPP, a behavioral serotonin syndrome was observed with both rCMRglc increases and decreases (25 mg/kg) or only rCMRglc increases (40 mg/kg). Whereas behavioral and metabolic activation induced by high doses of MCPP may result from stimulation at postsynaptic serotonin receptors, rCMRglc reductions and hypomotility produced by MCPP 2.5 mg/kg resemble the effects of serotonin receptor antagonists and suggest that, at this low dose, MCPP acts at modulatory serotonin autoreceptors to reduce endogenous serotonin release.