The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction

Guo, Yuan; Wang, Huiling; Xiang, Xiao-Hui; Zhao, Yan

doi:10.1016/j.neubiorev.2009.02.005

Cited by 45 publications

(38 citation statements)

References 207 publications

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“…Analysis of radiotracer metabolism in the plasma was performed from arterial blood samples collected at 3,8,15,30,60,90,120,180, and 240 minutes after injection and also from venous blood samples drawn at 60, 90, 120, 180, and 240 minutes after injection. Plasma metabolite analysis was performed using the column switching HPLC method 21 to determine the parent fraction.…”

Section: Input Functionmentioning

confidence: 99%

Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [¹⁸F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans

Sullivan

Lim

Labaree

et al. 2012

J Cereb Blood Flow Metab

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[ 18 F]FPEB is a positron emission tomography tracer which, in preclinical studies, has shown high specificity and selectivity toward the metabotropic glutamate receptor 5 (mGluR5). It possesses the potential to be used in human studies to evaluate mGluR5 function in a range of neuropsychiatric disorders, such as anxiety and Fragile X syndrome. To define optimal scan methodology, healthy human subjects were scanned for 6 hours following either a bolus injection (n ¼ 5) or bolus-plus-constant-infusion (n ¼ 5) of [ 18 F]FPEB. Arterial blood samples were collected and parent fraction measured by high-performance liquid chromatography (HPLC) to determine the metabolite-corrected plasma input function. Time activity curves were extracted from 13 regions and fitted by various models to estimate V T and BP ND . [ 18 F]FPEB was well fitted by the two-tissue compartment model, MA1 (t* ¼ 30), and MRTM (using cerebellum white matter as a reference). Highest V T values were observed in the anterior cingulate and caudate, and lowest V T values were observed in the cerebellum and pallidum. For kinetic modeling studies, V T and BP ND were estimated from bolus or bolus-plus-constant-infusion scans as short as 90 minutes. Bolus-plus-constant-infusion of [ 18 F]FPEB reduced intersubject variability in V T and allowed equilibrium analysis to be completed with a 30-minute scan, acquired 90-120 minutes after the start of injection.

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Section: Input Functionmentioning

confidence: 99%

Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [¹⁸F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans

Sullivan

Lim

Labaree

et al. 2012

J Cereb Blood Flow Metab

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“…Due to its' specific savoury taste "umami", it induces a "costumer's loyalty". It should be noted that corticostriatal glutamatergic transmission has role in stimulating the release of dopamine in the striatum, with implication in both the initiation and expression of addiction-related behaviors in addiction [3]. In our previous work, we demonstrated the addictive potential of MSG when given daily, in drinking water, to NMRI mice [4].…”

Section: Introductionmentioning

confidence: 99%

Experimental research on the interactions between some anxiolytics and dietary sodium monoglutamate

Buzescu

Cristea

Chiriac

et al. 2014

Acta Medica Marisiensis

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Objectives: Monosodium glutamate, the salt of glutamic acid, is largely used as a flavour enhancer (E621). In this study, we determine if monosodium glutamate, after repeated oral administration, can induce any degree of anxiety. Taking into account the interdependence between glutamate and GABA neurotransmissions, we studied the possible interactions of monosodium glutamate with some representatives belonging to benzodiazepines therapeutical class, diazepam and alprazolam, used as first line therapy for the treatment of anxiety. Methods: For determining the degree of anxiety, the specific cross-labyrinth test was used. The medium time spent in the closed-arms of the crosslabyrinth is correlated with increased anxiety and the medium time spent in the opened arms is correlated with a low degree anxiety. NMRI adult mice received 300 mg/kg monosodium glutamate for 21 days, dose representing 1/50 from mice LD50 (15000mg/kg) and twice the maximum admitted dose/ day for human. Results: When compared to control group, the group receiving monosodium glutamate, showed a not statistically significant slight increase in the degree of anxiety. The groups receiving benzodiazepines presented a significant reduction of the degree of anxiety, proving their anxiolytic effect. The groups receiving glutamate and diazepam or alprazolam, showed a lower reduction of the degree of anxiety, than group receiving only benzodiazepines, phenomenon which proves an antagonism between glutamate and the anxiolytics used in this study. Conclusions: The oral administration of monosodium glutamate increases slightly, not statistically significant, the degree of anxiety in mice and significantly alters the response to the benzodiazepines therapy, reducing the effect for both alprazolam and diazepam.

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“…MPEP | tolerance | respiratory depression T he excitatory neurotransmitter, glutamate, in the central nervous system (CNS) is an important mediator of opioid nociception, dependence, and withdrawal (1). Glutamate exerts its effect via two different classes of glutamate receptors: ionotropic and metabotropic.…”

mentioning

confidence: 99%

Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception

Akgün

Javed

Lunzer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The low effectiveness of morphine and related mu opioid analgesics for the treatment of chronic inflammatory pain is a result of opioid-induced release of proinflammatory cytokines and glutamate that lower the pain threshold. In this regard, the use of opioids with metabotropic glutamate-5 receptor (mGluR 5 ) antagonist has been reported to increase the efficacy of morphine and prevent the establishment of adverse effects during chronic use. Given the presence of opioid receptors (MORs) and mGluR 5 in glia and neurons, together with reports that suggest coexpressed MOR/mGluR 5 receptors in cultured cells associate as a heteromer, the possibility that such a heteromer could be a target in vivo was addressed by the design and synthesis of a series of bivalent ligands that contain mu opioid agonist and mGluR 5 antagonist pharmacophores linked through spacers of varying length (10-24 atoms). The series was evaluated for antinociception using the tail-flick and von Frey assays in mice pretreated with lipopolysaccharide (LPS) or in mice with bone cancer. In LPS-pretreated mice, MMG22 (4c, 22-atom spacer) was the most potent member of the series (intrathecal ED 50 ∼9 fmol per mouse), whereas in untreated mice its ED 50 was more than three orders of magnitude higher. As members of the series with shorter or longer spacers have ≥500-fold higher ED 50s in LPS-treated mice, the exceptional potency of MMG22 may be a result of the optimal bridging of protomers in a putative MOR-mGluR 5 heteromer. The finding that MMG22 possesses a >10 6 therapeutic ratio suggests that it may be an excellent candidate for treatment of chronic, intractable pain via spinal administration.MPEP | tolerance | respiratory depression T he excitatory neurotransmitter, glutamate, in the central nervous system (CNS) is an important mediator of opioid nociception, dependence, and withdrawal (1). Glutamate exerts its effect via two different classes of glutamate receptors: ionotropic and metabotropic. Among the metabotropic receptors (mGluRs), the receptor-5 subtype (mGluR 5 ) is widely distributed in the CNS (2), where it modulates synaptic transmission, neuronal excitability, and plasticity. The mGluR 5 is a class C G protein-coupled receptor (GPCR), the activation of which is mediated by binding of glutamate to its extracellular Venus flytrap domain. It is noteworthy that the selective mGluR 5 antagonist, 2-methyl-6-(phenylethynyl) pyridine (MPEP), acts allosterically by binding to the seven transmembrane (7TM) domain of the receptor (3).Reports of presence of the mu opioid receptor (MOR) and mGluR 5 in the spinal cord and the ability of coadministered MPEP and morphine to enhance morphine antinociception and suppress morphine-induced tolerance and dependence suggest a design strategy for the development of potent analgesics based on the targeting of both MOR and mGluR 5 (4-6). Given evidence (7) that supports the physical association of coexpressed MOR and mGluR 5 as heteromer (MOR-mGluR 5 ) in cultured cells, and the presence of MOR and mGluR 5 in t...

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The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction

Cited by 45 publications

References 207 publications

Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [¹⁸F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans

Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [¹⁸F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans

Experimental research on the interactions between some anxiolytics and dietary sodium monoglutamate

Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception

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The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction

Cited by 45 publications

References 207 publications

Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [18F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans

Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [18F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans

Experimental research on the interactions between some anxiolytics and dietary sodium monoglutamate

Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception

Contact Info

Product

Resources

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Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [¹⁸F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans

Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [¹⁸F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans