(S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord

Thomas, Nicola; Wright, Rebecca A.; Howson, Patrick A.; Kingston, Ann E.; Schoepp, Darryle D.; Jane, David E.

doi:10.1016/s0028-3908(00)00169-6

Cited by 134 publications

(118 citation statements)

References 22 publications

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“…Subtype-selective agonists for mGluR7 (AMN082) and mGluR8 (S-3,4-DCPG) (Ayala et al, 2008;Marabese et al, 2007;Mitsukawa et al, 2005;Schmid and Fendt, 2006;Stachowicz et al, 2005;Thomas et al, 2001) were administered into the CeA of normal animals and animals with arthritis induced in one knee by intraarticular injections of kaolin/ carrageenan. The key findings are as follows.…”

Section: Discussionmentioning

confidence: 99%

“…AMN082 and S-3,4-DCPG were dissolved in ACSF (vehicle) on the day of the experiment at a concentration 100 times that predicted to be needed in the tissue based on data in the literature (Marabese et al, 2007;Mitsukawa et al, 2005;Thomas et al, 2001) and our own in vitro studies in brain slices (Palazzo and Neugebauer, unpublished observations) because of the concentration gradient across the dialysis membrane (Fu and Neugebauer, 2008;Han et al, 2005b;Han and Neugebauer, 2005;. The numbers given in this article refer to the drug concentrations in the microdialysis fiber.…”

Section: Drugsmentioning

confidence: 99%

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Group III mGluR7 and mGluR8 in the amygdala differentially modulate nocifensive and affective pain behaviors

Palazzo

et al. 2008

Neuropharmacology

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SummaryThe amygdala plays an important role in the emotional-affective component of pain and in pain modulation. Group III metabotropic glutamate receptors (mGluRs) regulate pain-related activity in the amygdala, but the behavioral consequence and contribution of individual subtypes are not known yet. The present study determined the effects of mGluR7 and mGluR8 activation in the central nucleus of the amygdala (CeA) on nocifensive and affective pain responses and on pain-related anxiety-like behavior of adult rats. The pain state was induced by intraarticular injections of kaolin/carrageenan into one knee joint to produce a localized monoarthritis. Subtype-selective agonists were administered into the CeA by microdialysis in normal rats and in rats with arthritis. An mGluR7-selective agonist (N,N I -dibenzyhydryl-ethane-1,2-diamine dihydrochloride, AMN082, 25 µM) decreased spinal withdrawal reflex thresholds and increased audible and ultrasonic vocalizations evoked by brief (15 s) compression of the knee. AMN082 also decreased the open-arm preference in the elevated plus maze (EPM) test, suggesting anxiety-like behavior. In arthritic animals, however, AMN082 failed to modulate the increased spinal reflexes and vocalizations and anxiety-like behavior. An mGluR8-selective agonist (S-3,4-dicarboxyphenylglycine, S-3,4-DCPG, 10 µM) had no effect in normal animals but inhibited the increased spinal reflex responses and audible and ultrasonic vocalizations of arthritic rats. S-3,4-DCPG also increased the open-arm choices of arthritic rats, suggesting anxiolytic effects. The results suggest that under normal conditions mGluR7, but not mGluR8, facilitates pain responses and has anxiogenic properties whereas mGluR8, but not mGluR7, can inhibit nocifensive and affective behaviors and anxiety in a model of arthritic pain.

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Section: Discussionmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

Group III mGluR7 and mGluR8 in the amygdala differentially modulate nocifensive and affective pain behaviors

Palazzo

et al. 2008

Neuropharmacology

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“…This effect of DCPG was concentration dependent, with 10 and 30 mM DCPG inducing a depression that did not readily reverse (10 mM: 19.9±4.2 peak average percent depression; 30 mM: 16.6±3 peak average percent depression; representative single experiments in Figure 2a). At higher concentrations, DCPG loses selectivity for mGluR8 and can activate mGluR4 as well (Abitbol et al, 2008;Thomas et al, 2001). To determine whether mGluR4 was involved in mediating the effect of DCPG in the BNST, we repeated these experiments with the addition of PHCCC.…”

Section: Dcpg Depresses Excitatory Transmission In the Bnstmentioning

confidence: 99%

mGluR8 Modulates Excitatory Transmission in the Bed Nucleus of the Stria Terminalis in a Stress-Dependent Manner

Gosnell

Silberman

Grueter

et al. 2011

Neuropsychopharmacol

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Metabotropic glutamate receptors (mGluRs) are important modulators of excitatory transmission, and have been implicated in anxiety and stress-related behaviors. Previously, we showed that group III mGluR agonists could depress excitatory synaptic transmission in the bed nucleus of the stria terminalis (BNST), an integral component of the anxiety circuitry. Here, we provide converging evidence indicating that this effect is mediated primarily by mGluR8, is exerted presynaptically, and is modulated by noradrenergic signaling and stress. The effects of the group III mGluR agonist L-AP4 on excitatory transmission are not potentiated by the mGluR4-selective allosteric potentiator PHCCC, but are mimicked by the mGluR8-selective agonist DCPG. Consistent with these results, mGluR8-like immunoreactivity is seen in the BNST, and the actions of L-AP4 on excitatory transmission are absent in slices from mGluR8 knockout (KO) mice. Application of DCPG is associated with an increase in paired-pulse evoked glutamate synaptic currents, and a decrease in spontaneous glutamate synaptic current frequency, consistent with a primarily presynaptic action. mGluR8-mediated suppression of excitatory transmission is disrupted ex vivo by activation of a1 adrenergic receptors (a1 ARs). BNST mGluR8 function is also disrupted by both acute and chronic in vivo exposure to restraint stress, and in brain slices from a2A AR KO mice. These studies show that mGluR8 is an important regulator of excitatory transmission in the BNST, and suggest that this receptor is selectively disrupted by noradrenergic signaling and by both acute and chronic stress.

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“…However, recent efforts have provided novel pharmacological tools that provide greater selectivity between group III mGluR subtypes Mitsukawa et al, 2005;Thomas et al, 2001;Zhai et al, 2002) than previously available compounds. We have used these newer reagents to rigorously test the hypothesis that there is a developmental regulation of the presynaptic mGluR subtypes involved in regulating transmission at this synapse and to determine which mGluR subtypes mediate this effect at the different stages of postnatal development.…”

Section: Introductionmentioning

confidence: 99%

Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated

et al. 2008

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SummaryGroup III metabotropic glutamate receptors (mGluRs) reduce synaptic transmission at the Schaffer collateral-CA1 (SC-CA1) synapse in rats by a presynaptic mechanism. Previous studies show that low concentrations of the group III-selective agonist, L-AP4, reduce synaptic transmission in slices from neonatal but not adult rats, whereas high micromolar concentrations reduce transmission in both age groups. L-AP4 activates mGluRs 4 and 8 at much lower concentrations than those required to activate mGluR7, suggesting that the group III mGluR subtype modulating transmission is a high affinity receptor in neonates and a low affinity receptor in adults. The previous lack of subtype selective ligands has made it difficult to test this hypothesis. We have measured fEPSPs in the presence of novel subtype selective agents to address this question. We show that the effects of L-AP4 can be blocked by LY341495 in both neonates and adults, verifying that these effects are mediated by mGluRs. In addition, the selective mGluR8 agonist, DCPG, has a significant effect in slices from neonatal rats but does not reduce synaptic transmission in adult slices. The mGluR4 selective allosteric potentiator, PHCCC, is unable to potentiate the L-AP4-induced effects at either age. Taken together, our data suggest that group III mGluRs regulate transmission at the SC-CA1 synapse throughout development but there is a developmental regulation of the subtypes involved so that that both mGluR8 serves this role in neonates but not adults whereas mGluR7 is involved in regulating transmission at this synapse in throughout postnatal development.

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(S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord

Cited by 134 publications

References 22 publications

Group III mGluR7 and mGluR8 in the amygdala differentially modulate nocifensive and affective pain behaviors

Group III mGluR7 and mGluR8 in the amygdala differentially modulate nocifensive and affective pain behaviors

mGluR8 Modulates Excitatory Transmission in the Bed Nucleus of the Stria Terminalis in a Stress-Dependent Manner

Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated

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