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Glutamate Levels (glutamate + level)

Distribution by Scientific Domains

Life Sciences	57%
Medical Sciences	42%

Kinds of Glutamate Levels

extracellular glutamate level

Selected Abstracts

Glutamate levels and transport in cat (Felis catus) area 17 during cortical reorganization following binocular retinal lesions

JOURNAL OF NEUROCHEMISTRY, Issue 6 2003
Ann Massie
Abstract Glutamate is known to play a crucial role in the topographic reorganization of visual cortex after the induction of binocular central retinal lesions. In this study we investigated the possible involvement of the glial high-affinity Na+/K+ -dependent glutamate transporters in cortical plasticity using western blotting and intracortical microdialysis. Basal extracellular glutamate levels and the re-uptake activity for glutamate have been determined by comparing the extracellular glutamate concentration before and during the blockage of glutamate removal from the synaptic cleft with the potent transporter inhibitor l - trans -pyrrolidine-3,4-dicarboxylic acid. In cats with central retinal lesions we observed increased basal extracellular glutamate concentrations together with a decreased re-uptake activity in non-deprived, peripheral area 17, compared with the sensory-deprived, central cortex of the same animal as well as the topographically matching regions of area 17 in normal subjects. Western blotting experiments revealed a parallel decrease in the expression level of the glial glutamate transporter proteins GLT-1 and GLAST in non-deprived cortex compared with sensory-deprived cortex of lesion cats and the corresponding regions of area 17 of normal subjects. This study shows that partial sensory deprivation of the visual cortex affects the removal of glutamate from the synaptic cleft and implicates a role for glial,neuronal interactions in adult brain plasticity. [source]

Glutamate levels and activity of the T cell voltage-gated potassium Kv1.3 channel in patients with systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 5 2008
C. Poulopoulou
Objective Alterations in glutamate homeostasis and Kv1.3 voltage-gated potassium channel function have been independently associated with T cell dysfunction, whereas selective blockade of Kv1.3 channels inhibits T cell activation and improves T cell,mediated manifestations in animal models of autoimmunity. Because low extracellular glutamate concentrations enhance the activity of this channel in normal T cells ex vivo, we undertook this study to examine serum glutamate concentrations and Kv1.3 channel activity in patients with systemic lupus erythematosus (SLE). Methods We used high-performance liquid chromatography for glutamate measurements, and we used the whole-cell patch-clamp technique for electrophysiologic studies performed in freshly isolated, noncultured peripheral T cells. Results Mean ± SD serum concentrations of glutamate were lower in patients with either clinically quiescent SLE (77 ± 27 ,M [n = 18]) or active SLE (61 ± 36 ,M [n = 16]) than in healthy controls (166 ± 64 ,M [n = 24]) (both P < 0.0001). The intrinsic gating properties of the Kv1.3 channels in lupus T cells were found to be comparable with those in healthy control,derived T cells. Notably, electrophysiologic data from SLE patient,derived T cells exposed to extracellular glutamate concentrations similar to their respective serum levels (50 ,M) demonstrated Kv1.3 current responses enhanced by almost 20% (P < 0.01) compared with those subsequently obtained from the same cell in the presence of glutamate concentrations within control serum levels (200 ,M). Conclusion Based on the key role of Kv1.3 channel activity in lymphocyte physiology, an enhancing in vivo effect of low serum glutamate concentrations on the functional activity of this channel may contribute to lupus T cell hyperactivity. Studies to further elucidate Kv1.3 responses in SLE, as well as the possible pathogenetic role of this unsuspected metabolic abnormality, may have therapeutic implications for SLE patients. [source]

In vitro neurotoxic properties and excitatory aminoacids concentration in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010
Relationship with the degree of certainty of disease diagnoses
Fiszman ML, Ricart KC, Latini A, Rodríguez G, Sica REP. In vitro neurotoxic properties and excitatory aminoacids concentration in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Relationship with the degree of certainty of disease diagnoses. Acta Neurol Scand: 2010: 121: 120,126. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To determine glutamate and aspartate levels in the cerebrospinal fluid (CSF) in patients with sporadic amyotrophic lateral sclerosis (SALS) grouped according to El Escorial diagnostic criteria, and to perform an in vitro assessment of the neurotoxicity of the CSF in murine cortical neurons. Methods,,, SALS patients were sorted according to El Escorial diagnostic criteria. Glutamate and aspartate were measured in the CSF using high performance liquid chromatography. Cultured cortical neuron viability was determined after exposure to CSF for 24 h. Results,,, Glutamate levels were elevated in 28 out of the 29 patients with definite, probable or possible SALS. There were no differences in glutamate concentrations when the three clinical forms of the disease were compared; neither there were significant variation across disease duration and clinical presentation. In agreement with previous reports, we concluded that CSF-SALS-induced in vitro neurotoxicity is mediated by ionotropic glutamate receptors. We found no relationship between the degree of in vitro neurotoxicity and glutamate concentration in the CSF. Conclusions,,, Glutamate but not aspartate CSF levels may contribute to ALS pathogenesis. However, glutamate levels may not influence the degree of diagnosis certainty or lesion extension. [source]

Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients

EPILEPSIA, Issue 8 2008
Idil Cavus
Summary Purpose: Temporal lobe epilepsy (TLE) is associated with smaller hippocampal volume and with elevated extracellular (EC) glutamate levels. We investigated the relationship between the hippocampal volume and glutamate in refractory TLE patients. Methods: We used quantitative MRI volumetrics to measure the hippocampal volume and zero-flow microdialysis to measure the interictal glutamate, glutamine, and GABA levels in the epileptogenic hippocampus of 17 patients with medication-resistant epilepsy undergoing intracranial EEG evaluation. The relationships between hippocampal volume, neurochemical levels, and relevant clinical factors were examined. Results: Increased EC glutamate in the epileptogenic hippocampus was significantly related to smaller ipsilateral (R2= 0.75, p < 0.0001), but not contralateral hippocampal volume when controlled for glutamine and GABA levels, and for clinical factors known to influence hippocampal volume. Glutamate in the atrophic hippocampus was significantly higher (p = 0.008, n = 9), with the threshold for hippocampal atrophy estimated as 5 ,M. GABA and glutamine levels in the atrophic and nonatrophic hippocampus were comparable. Decreased hippocampal volume was related to higher seizure frequency (p = 0.008), but not to disease duration or febrile seizure history. None of these clinical factors were related to the neurochemical levels. Conclusions: We provide evidence for a significant association between increased EC glutamate and decreased ipsilateral epileptogenic hippocampal volume in TLE. Future work will be needed to determine whether the increase in glutamate has a causal relationship with hippocampal atrophy, or whether another, yet unknown factor results in both. This work has implications for the understanding and treatment of epilepsy as well as other neurodegenerative disorders associated with hippocampal atrophy. [source]

Cocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course study

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004
Jason M. Williams
Abstract Excitatory amino acid transmission within mesocorticolimbic brain pathways is thought to play an important role in behavioural sensitization to psychomotor stimulants. The current studies evaluated a time course of the effects of cocaine on extracellular glutamate levels within the medial prefrontal cortex (mPFC) following increasing periods of withdrawal from repeated cocaine exposure. Male Sprague,Dawley rats underwent stereotaxic surgeries and were pretreated daily with saline (1 mL/kg/day × 4 days, i.p.) or cocaine (15 mg/kg/day × 4 days, i.p.) and withdrawn for 1, 7 or 30 days. After withdrawal rats were challenged with the same dose of saline or cocaine and in vivo microdialysis of the mPFC was conducted with concurrent analysis of locomotor activity. Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine-induced mPFC glutamate levels compared to saline and acute control subjects, which were similarly unaffected by cocaine challenge. At the 7 day time point, a subset of animals that received repeated cocaine did not express behavioural sensitization, nor did these animals exhibit the enhancement in mPFC glutamate in response to cocaine challenge. In contrast to these early effects, 30 days of withdrawal resulted in no significant changes in cocaine-induced mPFC glutamate levels regardless of the pretreatment or behavioural response. These data suggest that repeated cocaine administration transiently increases cocaine-induced glutamate levels in the mPFC during the first week of withdrawal, which may play an important role in the development of behavioural sensitization to cocaine. [source]

Intravenous heroin self-administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004
Stéphanie Caillé
Abstract Several lines of evidence suggest that opiate-induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self-administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self-administration (0.02 mg per infusion; FR-1), and remained ,,65% of presession baseline levels for the remainder of the 3-h self-administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of ,,120% presession values during the subsequent 2 h of self-administration. Thus, heroin self-administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self-administration results in a disinhibition and/or excitation of the ventral pallidum. [source]

High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003
Peter Somogyi
Abstract The release of neurotransmitters is modulated by presynaptic metabotropic glutamate receptors (mGluRs), which show a highly selective expression and subcellular location in glutamatergic terminals in the hippocampus. Using immunocytochemistry, we investigated whether one of the receptors, mGluR7, whose level of expression is governed by the postsynaptic target, was present in GABAergic terminals and whether such terminals targeted particular cells. A total of 165 interneuron dendritic profiles receiving 466 synapses (82% mGluR7a-positive) were analysed. The presynaptic active zones of most GAD-(77%) or GABA-positive (94%) synaptic boutons on interneurons innervated by mGluR7a-enriched glutamatergic terminals (mGluR7a-decorated) were immunopositive for mGluR7a. GABAergic terminals on pyramidal cells and most other interneurons in str. oriens were mGluR7a-immunonegative. The mGluR7a-decorated cells were mostly somatostatin- and mGluR1,-immunopositive neurons in str. oriens and the alveus. Their GABAergic input mainly originated from VIP-positive terminals, 90% of which expressed high levels of mGluR7a in the presynaptic active zone. Parvalbumin-positive synaptic terminals were rare on mGluR7a-decorated cells, but on these neurons 73% of them were mGluR7a-immunopositive. Some type II synapses innervating interneurons were immunopositive for mGluR7b, as were some type I synapses. Because not all target cells of VIP-positive neurons are known it has not been possible to determine whether mGluR7 is expressed in a target-cell-specific manner in the terminals of single GABAergic cells. The activation of mGluR7 may decrease GABA release to mGluR7-decorated cells at times of high pyramidal cell activity, which elevates extracellular glutamate levels. Alternatively, the presynaptic receptor may be activated by as yet unidentified endogenous ligands released by the GABAergic terminals or the postsynaptic dendrites. [source]

Alterations in behaviour and glutamate transmission following presentation of stimuli previously associated with cocaine exposure

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001
Gregory Hotsenpiller
Abstract To study the role of glutamate in cocaine-conditioned responses, we developed a rat model in which conditioned locomotion is produced by repeated pairing of cocaine with discrete stimuli (flashing light and metronome). ,Paired' subjects received cocaine (15 mg/kg) prior to six exposures to stimuli for 30 min in the test environment. ,Unpaired' subjects received equivalent presentations of the stimuli yet received cocaine in home cages. Tests with the stimuli alone demonstrated that the conditioned locomotion displayed by Paired subjects was evident at 3 or 10 days post-training and resistant to two sessions of testing. The degree of conditioned locomotion was not correlated with the subjects' response to novelty or cocaine. Administration of the noncompetitive AMPA receptor antagonist GYKI 52466 (2.5 mg/kg, a dose without effect on spontaneous activity) attenuated the expression of conditioned activity. In vivo microdialysis revealed that Paired subjects had significantly lower basal glutamate levels in the nucleus accumbens (NAc) than did Unpaired subjects when no stimuli were presented. Presentation of the conditioned stimuli resulted in significant increases in glutamate levels in the NAc in the Paired group whilst glutamate levels in the Unpaired group remained unchanged. The associative control of glutamate levels in the NAc by stimuli formerly paired with a drug of abuse is an unprecedented finding. It is likely to reflect the convergence of excitatory inputs that the NAc receives from limbic structures. [source]

Altered striatal amino acid neurotransmitter release monitored using microdialysis in R6/1 Huntington transgenic mice

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001
B. NicNiocaill
Abstract Huntington's disease is an autosomal dominant disease which presents with striatal and cortical degeneration causing involuntary movements, dementia and emotional changes. We employed 16-week-old transgenic Huntington mice (R6/1 line developed by Bates and coworkers) that express exon 1 of the mutant human Huntington gene with 115 CAG triplet repeats. At this age, R6/1 mice do not exhibit an overt neurological phenotype nor any striatal neuronal loss. Using microdialysis, we monitored basal and intrastriatal N-methyl d -aspartate (NMDA, 100 µm, 15 min)- and KCl (100 mm, 15 min)-induced increases in local aspartate, glutamate and GABA release in halothane-anaesthetized transgenic mice and wild-type controls. Basal striatal dialysate glutamate levels were reduced by 42% in R6/1 mice whilst aspartate and GABA levels did not differ from those observed in control mice. Intrastriatal NMDA was associated with significantly greater aspartate (at 15 min) and GABA (at 30 min) levels in the R6/1 mice compared to controls, whilst glutamate release rapidly increased to the same extent in both groups. Intrastriatal KCl was associated with enhanced increases (30 min) in local aspartate and glutamate release in the R6/1 mice above those observed in controls whilst the rapid increase (15 min) in GABA release was similar in both groups. The results provide compelling evidence for specific alterations in both basal, as well as NMDA- and KCl-induced, release of striatal amino acid neurotransmitters in this transgenic model of Huntington's disease, even in the absence of manifest neurodegeneration. [source]

Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia

GENES, BRAIN AND BEHAVIOR, Issue 5 2005
K. K. Szumlinski
Homer proteins are involved in the functional assembly of postsynaptic density proteins at glutamatergic synapses and are implicated in learning, memory and drug addiction. Here, we report that Homer1 -knockout (Homer1 -KO) mice exhibit behavioral and neurochemical abnormalities that are consistent with the animal models of schizophrenia. Relative to wild-type mice, Homer1 -KO mice exhibited deficits in radial arm maze performance, impaired prepulse inhibition, enhanced ,behavioral despair', increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced MK-801- and methamphetamine-stimulated motor behavior. No-net-flux in vivo microdialysis revealed a decrease in extracellular glutamate content in the nucleus accumbens and an increase in the prefrontal cortex. Moreover, in Homer1 -KO mice, cocaine did not stimulate a rise in frontal cortex extracellular glutamate levels, suggesting hypofrontality. These behavioral and neurochemical data derived from Homer1 mutant mice are consistent with the recent association of schizophrenia with a single-nucleotide polymorphism in the Homer1 gene and suggest that the regulation of extracellular levels of glutamate within limbo-corticostriatal structures by Homer1 gene products may be involved in the pathogenesis of this neuropsychiatric disorder. [source]

Glutamate spillover augments GABA synthesis and release from axodendritic synapses in rat hippocampus

HIPPOCAMPUS, Issue 1 2010
Misty M. Stafford
Abstract Tight coupling between gamma-aminobutyric acid (GABA) synthesis and vesicle filling suggests that the presynaptic supply of precursor glutamate could dynamically regulate inhibitory synapses. Although the neuronal glutamate transporter excitatory amino acid transporter 3 (EAAT3) has been proposed to mediate such a metabolic role, highly efficient astrocytic uptake of synaptically released glutamate normally maintains low-extracellular glutamate levels. We examined whether axodendritic inhibitory synapses in stratum radiatum of hippocampal area CA1, which are closely positioned among excitatory glutamatergic synapses, are regulated by synaptic glutamate release via presynaptic uptake. Under conditions of spatially and temporally coordinated release of glutamate and GABA within pyramidal cell dendrites, blocking glial glutamate uptake enhanced quantal release of GABA in a transporter-dependent manner. These physiological findings correlated with immunohistochemical studies revealing expression of EAAT3 by interneurons and uptake of D-asparate into putative axodendritic inhibitory terminals only when glial uptake was blocked. These results indicate that spillover of glutamate between adjacent excitatory and inhibitory synapses can occur under conditions when glial uptake incompletely clears synaptically released glutamate. Our anatomical studies also suggest that perisomatic inhibitory synapses, unlike synapses within dendritic layers of hippocampus, are not capable of glutamate uptake and therefore transporter-mediated dynamic regulation of inhibition is a unique feature of axodendritic synapses that may play a role in maintaining a homeostatic balance of inhibition and excitation. © 2009 Wiley-Liss, Inc. [source]

Changes of bladder activity and glycine levels in the lumbosacral cord after partial bladder outlet obstruction in rats

INTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2008
Minoru Miyazato
Objectives: We investigated the time course of changes in bladder activity as well as in spinal and serum levels of glutamate and glycine after partial bladder outlet obstruction (BOO) in rats. Methods: A total of 36 female rats were divided into six groups: sham operation (control); 3 days, 14 days, and 28 days after BOO; 3 days and 28 days after relief of BOO. Under urethane anesthesia, isovolumetric cystometry was carried out in each group. Then, spinal and serum levels of glutamate and glycine were measured. Results: The interval between bladder contractions was shorter in all of the groups compared with the control group. The amplitude and duration of bladder contractions was decreased at 3 days, 14 days, and 28 days after BOO, and at 3 days after relief of BOO. Spinal and serum glutamate levels showed no changes. However, the spinal glycine level was decreased at 14 days and 28 days after BOO, and at 28 days after relief of BOO. Serum glycine level was also decreased at 28 days after BOO and 28 days after relief of BOO. Conclusions: Detrusor overactivity during the chronic phase of partial BOO is partly caused by a decrease of glycinergic neuronal activity in the lumbosacral cord. A 3-day period of BOO produces detrusor overactivity, which might be due to an irreversible decrease of spinal glycinergic neuronal activity. [source]

The position of an arginine residue influences substrate affinity and K+ coupling in the human glutamate transporter, EAAT1

JOURNAL OF NEUROCHEMISTRY, Issue 2 2010
Renae M. Ryan
J. Neurochem. (2010) 114, 565,575. Abstract Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and extracellular glutamate levels are controlled by a family of transporters known as excitatory amino acid transporters (EAATs). The EAATs transport glutamate and aspartate with similar micromolar affinities and this transport is coupled to the movement of Na+, K+, and H+. The crystal structure of a prokaryotic homologue of the EAATs, aspartate transporter from Pyrococcus horokoshii (GltPh), has yielded important insights into the architecture of this transporter family. GltPh is a Na+ -dependent transporter that has significantly higher affinity for aspartate over glutamate and is not coupled to H+ or K+. The highly conserved carboxy-terminal domains of the EAATs and GltPh contain the substrate and ion binding sites, however, there are a couple of striking differences in this region that we have investigated to better understand the transport mechanism. An arginine residue is in close proximity to the substrate binding site of both GltPh and the EAATs, but is located in transmembrane domain (TM) 8 in the EAATs and hairpin loop 1 (HP1) of GltPh. Here we report that the position of this arginine residue can explain some of the functional differences observed between the EAATs and GltPh. Moving the arginine residue from TM8 to HP1 in EAAT1 results in a transporter that has significantly increased affinity for both glutamate and aspartate and is K+ independent. Conversely, moving the arginine residue from HP1 to TM8 in GltPh results in a transporter that has reduced affinity for aspartate. [source]

Glial connexins and gap junctions in CNS inflammation and disease

JOURNAL OF NEUROCHEMISTRY, Issue 3 2008
Tammy Kielian
Abstract Gap junctions facilitate direct cytoplasmic communication between neighboring cells, facilitating the transfer of small molecular weight molecules involved in cell signaling and metabolism. Gap junction channels are formed by the joining of two hemichannels from adjacent cells, each composed of six oligomeric protein subunits called connexins. Of paramount importance to CNS homeostasis are astrocyte networks formed by gap junctions, which play a critical role in maintaining the homeostatic regulation of extracellular pH, K+, and glutamate levels. Inflammation is a hallmark of several diseases afflicting the CNS. Within the past several years, the number of publications reporting effects of cytokines and pathogenic stimuli on glial gap junction communication has increased dramatically. The purpose of this review is to discuss recent observations characterizing the consequences of inflammatory stimuli on homocellular gap junction coupling in astrocytes and microglia as well as changes in connexin expression during various CNS inflammatory conditions. [source]

Glutamate levels and transport in cat (Felis catus) area 17 during cortical reorganization following binocular retinal lesions

ENT1 Regulates Ethanol-Sensitive EAAT2 Expression and Function in Astrocytes

ALCOHOLISM, Issue 6 2010
Jinhua Wu
Background:, Equilibrative nucleoside transporter 1 (ENT1) and excitatory amino acid transporter 2 (EAAT2) are predominantly expressed in astrocytes where they are thought to regulate synaptic adenosine and glutamate levels. Because mice lacking ENT1 display increased glutamate levels in the ventral striatum, we investigated whether ENT1 regulates the expression and function of EAAT2 in astrocytes, which could contribute to altered glutamate levels in the striatum. Methods:, We examined the effect of ENT1 inhibition and overexpression on the expression of EAAT2 using quantitative real-time PCR and measured glutamate uptake activity in cultured astrocytes. We also examined the effect of 0 to 200 mM ethanol doses for 0 to 24 hours of ethanol exposure on EAAT2 expression and glutamate uptake activity. We further examined the effect of ENT1 knockdown by a specific siRNA on ethanol-induced EAAT2 expression. Results:, An ENT1-specific antagonist and siRNA treatments significantly reduced both EAAT2 expression and glutamate uptake activity while ENT1 overexpression up-regulated EAAT2 mRNA expression. Interestingly, 100 or 200 mM ethanol exposure increased EAAT2 mRNA expression as well as glutamate uptake activity. Moreover, we found that ENT1 knockdown inhibited the ethanol-induced EAAT2 up-regulation. Conclusions:, Our results suggest that ENT1 regulates glutamate uptake activity by altering EAAT2 expression and function, which might be implicated in ethanol intoxication and preference. [source]

Acamprosate: Recent Findings and Future Research Directions

ALCOHOLISM, Issue 7 2008
Karl Mann
This article explores the mechanisms of action and the potential responder profile of acamprosate, a compound efficacious in relapse prevention of alcoholism. New evidence at the molecular and cellular level suggests that acamprosate attenuates hyper-glutamatergic states that occur during early abstinence and involves iono (NMDA)- and metabotrotropic (mGluR5) glutamate receptors along with augmented intracellular calcium release and electrophysiological changes. Thus mutant mice with enhanced glutamate levels exhibit higher alcohol consumption than wild type mice and respond better to acamprosate, demonstrating that acamprosate acts mainly on a hyper-glutamatergic system. This mode of action further suggests that acamprosate exhibits neuroprotective properties. In rats, cue-induced reinstatement behavior is significantly reduced by acamprosate treatment whereas cue-induced craving responses in alcohol-dependent patients seem not to be affected by this treatment. An ongoing study ("Project Predict") defines specific responder profiles for an individualized use of acamprosate and naltrexone. Neurophysiological as well as psychometric data are used to define 2 groups of patients: "reward cravers" and "relief cravers". While naltrexone should work better in the first group, acamprosate is hypothesized to be efficacious in the latter where withdrawal associated and/or cue induced hyper-glutamatergic states are thought to trigger relapse. Further research should target the definition of subgroups applying endophenotypic approaches, e.g. by detecting a hyperglutamatergic syndrome using MR spectroscopy. [source]

Effects of Acamprosate on Excitatory Amino Acids During Multiple Ethanol Withdrawal Periods

ALCOHOLISM, Issue 3 2003
Abdelkader Dahchour
Background: Our previous studies on the effects of acamprosate on enhanced locomotion during repeated withdrawals are now extended to the effects of acamprosate on excitatory amino acids in the hippocampus during repeated ethanol withdrawals. Methods: In this study, Wistar rats were made ethanol dependent by 4 weeks of vapor inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 hr withdrawals and 1 week of chronic ethanol treatment. The microdialysis technique was used together with high-performance liquid chromatography and electrochemical detection to quantify different amino acids such as aspartate and glutamate. Results: An intraperitoneal administration of acamprosate (400 mg/kg) to naïve rats did not alter aspartate or glutamate levels compared with the saline groups. During the first cycle of ethanol withdrawal, the administration of acamprosate (400 mg/kg, intraperitoneally) 2 hr after the commencement of ethanol withdrawal decreased both aspartate and glutamate microdialysate levels when compared with their respective saline group. Acamprosate administration also significantly decreased glutamate levels during the third withdrawal compared with the saline group, whereas no changes were seen in aspartate levels. Conclusion: The results of this work demonstrate that acamprosate reduced the excitatory amino acid glutamate increase observed during repeated ethanol withdrawal. These effects of acamprosate may provide a protective mechanism against neurotoxicity by reducing excitatory amino acids, particularly glutamate. [source]