Characterisation of an mGlu8 receptor-selective agonist and antagonist in the lateral and medial perforant path inputs to the dentate gyrus

Mercier, Marion; Lodge, David; Fang, Guangyu; Nicolas, Céline S.; Collett, Valerie J.; Jane, David E.; Collingridge, Graham L.; Bortolotto, Zuner A.

doi:10.1016/j.neuropharm.2012.11.020

Cited by 15 publications

(9 citation statements)

References 44 publications

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“…Intriguingly, a single administration of MDCPG did not changed the fEPSPs in sham mice, whereas it increased both the amplitude and the slope of basal fEPSPs, thus saturating and preventing the further potentiation after TBS in SNI mice. This is in line with the observation that MDCPG, even if administered at a lower concentration than that used in the current study, failed to modify fEPSP amplitude in the LEC-DG pathway in hippocampal slices from normal rats [67]. However, MDCPG prevented the LTP induction in SNI mice chronically treated with PEA.…”

Section: Discussionsupporting

confidence: 92%

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Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated with Neuropathic Pain

Boccella

Marabese

Iannotta

et al. 2019

IJMS

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This study investigated whether metabotropic glutamate receptor (mGluR) 5 and 8 are involved in the effect of ultramicronizedpalmitoylethanolamide (um-PEA) on the cognitive behavior and long term potentiation (LTP) at entorhinal cortex (LEC)-dentate gyrus (DG) pathway in mice rendered neuropathic by the spare nerve injury (SNI). SNI reduced discriminative memory and LTP. Um-PEA treatment started after the development of neuropathic pain had no effects in sham mice, whereas it restored cognitive behavior and LTP in SNI mice. 2-Methyl-6-(phenylethynyl) pyridine (MPEP), a selective mGluR5 antagonist, improved cognition in SNI mice and produced a chemical long term depression of the field excitatory postsynaptic potentials (fEPSPs) in sham and SNI mice. After theta burst stimulation (TBS) MPEP restored LTP in SNI mice. In combination with PEA, MPEP antagonized the PEA effect on discriminative memory and decreased LTP in SNI mice. The (RS)-4-(1-amino-1-carboxyethyl)phthalic acid (MDCPG), a selective mGluR8 antagonist, did not affect discriminative memory, but it induced a chemical LTP and prevented the enhancement of fEPSPs after TBS in SNI mice which were treated or not treated with PEA. The effect of PEA on LTP and cognitive behavior was modulated by mGluR5 and mGluR8. In particular in the SNI conditions, the mGluR5 blockade facilitated memory and LTP, but prevented the beneficial effects of PEA on discriminative memory while the mGluR8 blockade, which was ineffective in itself, prevented the favorable action of the PEA on LTP. Thus, although their opposite roles (excitatory/inhibitory of the two receptor subtypes on the glutamatergic system), they appeared to be required for the neuroprotective effect of PEA in conditions of neuropathic pain.

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Section: Discussionsupporting

confidence: 92%

“…Drugs were dissolved in 0.05% dimethylsulfoxide in artificial cerebrospinal fluid (ACSF) on the day of the experiment. The dose of drugs was chosen according to our and otherin vivoandex vivostudies [17,18,27,33,47,67,74,75,76].…”

Section: Methodsmentioning

confidence: 99%

Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated with Neuropathic Pain

Boccella

Marabese

Iannotta

et al. 2019

IJMS

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“…However, DCPG is only marginally selective for mGluR8 because high concentrations of DCPG also activate the mGluR2 (Mercier et al . ). The effects of DCPG have been investigated so far in the amygdala, PAG, dorsal striatum, and NTS.…”

Section: Group III Mglurs and Painmentioning

confidence: 97%

Nociception modulation by supraspinal group III metabotropic glutamate receptors

Palazzo

Marabese

Luongo

et al. 2017

Journal of Neurochemistry

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The modulatory actions of glutamate, the main excitatory neurotransmitter in the central nervous system (CNS), are exerted through the activation of metabotropic glutamate receptors (mGluRs). Of the eight known mGluRs (mGluR1-8), group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8) are less understood because of the lack of selective ligands. Except for mGluR6, group III mGluRs are widely distributed throughout the CNS. They are mainly located on presynaptic terminals where they inhibit neurotransmitter release at glutamatergic and caminobutyric acid (GABA)ergic synapses. Their location at certain synapses is considered critical for normal CNS function, which makes them potential targets in neurological and psychiatric treatments. Novel ligands that are selective for group III mGluR subtypes have recently been developed. These compounds, which mainly target allosteric sites and act as positive or negative allosteric modulators (PAMs or NAMs) of glutamate transmission, are contributing to the understanding of the functional roles of group III mGluRs in a number of pathological conditions, such as epilepsy, anxiety, neurodegenerative diseases, and chronic pain. Moreover, the presence of group III mGluRs throughout the entire pain neuraxis and particularly in the descending system suggests that these endogenous substrates that extend from the cortex to the first spinal synapse are candidates for pain control. Recent data on chronic pain alleviation by group III mGluR ligands encourage further studies as pathological pain is one of the most troublesome diseases because of the current lack of satisfactory therapy. This review summarizes recent studies on group III mGluRs in animal models of chronic pain, which evidence an opposite modulation of mGluR7 and mGluR8 on pain responses and their capability to affect pain responses only in pathological states.

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“…Parasagittal hippocampal slices (400 μM) were prepared, and experiments carried out in submerged conditions and at a temperature of 28 À 30°C, as described previously. [28] Briefly, field excitatory postsynaptic potentials (fEPSPs) were evoked at 0.03 Hz using a bipolar stimulating electrode, and recorded using glass micropipettes pulled to a resistance of 3-6 MΩ and filled with 3 M NaCl. Both electrodes were positioned in stratum radiatum of area CA1, and NMDA-fEPSPs were isolated by addition of picrotoxin (50 μM), CGP 55845 hydrochloride (1 μM) and NBQX (10 μM) to the perfusate, in order to block GABA-A, GABA-B and AMPA/kainate receptors, respectively.…”

Section: Electrophysiologymentioning

confidence: 99%

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

Wallach

Kavanagh

McLaughlin

et al. 2014

Drug Testing and Analysis

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Substances with the diphenylethylamine nucleus represent a recent addition to the product catalog of dissociative agents sold as ‘research chemicals’ on the Internet. Diphenidine, i.e. 1‐(1,2‐diphenylethyl)piperidine (1,2‐DEP), is such an example but detailed analytical data are less abundant. The present study describes the synthesis of diphenidine and its most obvious isomer, 1‐(2,2‐diphenylethyl)piperidine (2,2‐DEP), in order to assess the ability to differentiate between them. Preparation and characterization were also extended to the two corresponding pyrrolidine analogues 1‐(1,2‐diphenylethyl)‐ and 1‐(2,2‐diphenylethyl)pyrrolidine, respectively. Analytical characterizations included high‐resolution electrospray mass spectrometry (HR‐ESI‐MS), liquid chromatography ESI‐MS/MS, gas chromatography ion trap electron and chemical ionization MS, nuclear magnetic resonance spectroscopy (NMR) and infrared spectroscopy. Differentiation between the two isomeric pairs was possible under GC‐(EI/CI)‐MS conditions and included the formation of distinct iminium ions, such as m/z 174 for 1,2‐DEP and m/z 98 for 2,2‐DEP, respectively. The pyrrolidine counterparts demonstrated similar phenomena including the expected mass difference of 14 Da due to the lack of one methylene unit in the ring. Two samples obtained from an Internet vendor provided confirmation that diphenidine was present in both samples, concurring with the product label. Finally, it was confirmed that diphenidine (30 μM) reduced N‐methyl‐D‐aspartate‐mediated field excitatory postsynaptic potentials (NMDA‐fEPSPs) to a similar extent to that of ketamine (30 μM) when using rat hippocampal slices. The appearance of 1,2‐ diphenylethylamines appears to reflect the exploration of alternatives to arylcyclohexylamine‐type substances, such as methoxetamine, PCP and PCPy‐based analogues that also show NMDA receptor activity as demonstrated here for diphenidine. Copyright © 2014 John Wiley & Sons, Ltd.

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Characterisation of an mGlu8 receptor-selective agonist and antagonist in the lateral and medial perforant path inputs to the dentate gyrus

Cited by 15 publications

References 44 publications

Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated with Neuropathic Pain

Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated with Neuropathic Pain

Nociception modulation by supraspinal group III metabotropic glutamate receptors

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

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