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Biomedical subjects

T E Salt

Publications and source records attributed to T E Salt.

At least 19 recordsLinked to original sources
PubMed2006

Retinal repair by transplantation of photoreceptor precursors.

Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system repair; photoreceptor degeneration initially leaves the inner retinal circuitry intact and new photoreceptors need only make single, short synaptic connections to contribute to the retinotopic map. So far, brain- and retina-derived stem cells transplanted into adult retina have shown little evidence of being able to integrate into the outer nuclear layer and differentiate into new photoreceptors. Furthermore, there has been no demonstration that transplanted cells form functional synaptic connections with other neurons in the recipient retina or restore visual function. This might be because the mature mammalian retina lacks the ability to accept and incorporate stem cells or to promote photoreceptor differentiation. We hypothesized that committed progenitor or precursor cells at later ontogenetic stages might have a higher probability of success upon transplantation. Here we show that donor cells can integrate into the adult or degenerating retina if they are taken from the developing retina at a time coincident with the peak of rod genesis. These transplanted cells integrate, differentiate into rod photoreceptors, form synaptic connections and improve visual function. Furthermore, we use genetically tagged post-mitotic rod precursors expressing the transcription factor Nrl (ref. 6) (neural retina leucine zipper) to show that successfully integrated rod photoreceptors are derived only from immature post-mitotic rod precursors and not from proliferating progenitor or stem cells. These findings define the ontogenetic stage of donor cells for successful rod photoreceptor transplantation.

Animals↗
PubMed2006

Modulation of GABAergic inhibition in the rat superior colliculus by a presynaptic group II metabotropic glutamate receptor.

Previous work has indicated that metabotropic glutamate receptors (mGluRs) modulate visual responses of superior colliculus (SC) neurones in vivo in a variety of ways, in a manner that can be dependent upon visual stimulus properties. How this occurs remains unclear. In this study we aimed to determine how activation of mGluR2 and mGluR3 receptors (Group II) might modulate visual responses, by using field potential and whole-cell patch clamp recording techniques in rat SC slice. Stimulation within the superficial layers of the SC, in the presence of ionotropic glutamate receptor antagonists, evoked IPSCs that were blocked by bicuculline indicating that they are mediated via GABAA receptors. It is likely that these IPSCs were of heterogeneous origin as they showed substantial variation in paired-pulse behaviour. Nevertheless, activation of Group II mGluRs with the group-selective agonist LY354740 (300 nM, bath application) resulted in a reduction of these IPSCs (to 56% of control amplitude), and this was associated with a decrease in paired-pulse depression. At the same concentration, LY354740 did not reduce the EPSC or field-EPSP evoked by stimulation of the retinal input to the SC. The effects of LY354740 on IPSCs were not mimicked by the mGluR3-selective agonist N-acetyl-aspartyl-glutamate (NAAG, 200-500 microM). Stimulation of IPSCs with trains of impulses (10 at 20 Hz) in order to mimic natural activation patterns resulted in sequences of IPSCs that were reduced in amplitude towards the end of the stimulus train. Application of the Group II antagonist LY341495 (100 nM) under these conditions resulted in an increase in later IPSCs in a third of neurones tested. These findings indicate that mGluR2 (but not mGluR3) can selectively modulate GABAergic inhibition in SC, probably via a presynaptic mechanism. Furthermore, these receptors may be activated by synaptically released transmitter during patterns of activation similar to those seen during visual processing. Thus mGluR2 receptors could have a function in activity-dependent modulation of inhibitory processing during visual responses.

Animals↗
PubMed2005

Changes in glutamate receptor function in synaptic input to the superficial superior colliculus (SSC) with aging and in retinal degeneration in the Royal College of Surgeons (RCS) rat.

Ionotropic and metabotropic glutamate receptors mediate and modulate retinocollicular transmission. The Royal College of Surgeons (RCS) dystrophic strain of rats suffers from a progressive retinal degeneration with age and hence loss of visual function. We investigated whether this loss of function is accompanied by functional changes in a central target of retinal axons, the superficial superior colliculus (SSC). Field potential recordings were made in SSC slices from RCS rats aged either 4-7 weeks or 33-52 weeks. Blockade of GABAergic transmission revealed a field EPSP in response to optic tract stimulation which was sensitive to the NMDA antagonist AP5. In normal non-dystrophic rats the contribution of NMDA receptors to the fEPSP declined with age, whereas in dystrophic animals no such decline was seen. As mGluR8 may be located on terminals of retinal axons, we also assessed the function of this receptor. The mGluR8 agonist DCPG reduced fEPSPs in normal and dystrophic rats in both age groups to a similar extent, although the effect of DCPG declined with age. These findings indicate that the contribution of NMDA receptors to retinocollicular transmission declines with age in normal rats, but that such a decline is not seen in dystrophic rats which have severely reduced visual function. As NMDA receptors are associated with neural plasticity, it may be that this finding represents an increased residual potential for plasticity in dystrophic rats which may be functionally important.

Aging↗
PubMed2005

Modulation of retino-collicular transmission by Group III metabotropic glutamate receptors at different ages during development.

Group III metabotropic glutamate receptors (especially mGlu4, mGlu7, mGlu8) are thought to be involved in modulating visual processing in the adult superior colliculus, a major termination site of retinal input in the rodent brain. We have investigated this role by making field EPSP recordings in response to optic tract stimulation in superior colliculus slices taken from rats aged from P14 to P180. Application of the Group III agonist L-AP4 at a concentration (10 microM) effective to activate mGlu4 and mGlu8 receptors, but not mGlu7 receptors, resulted in reductions of the field EPSP in all ages, although the effect was greatest in slices taken from P14 rats. Increasing the L-AP4 concentration to 100 microM so as to also activate mGlu7 receptors resulted in further field EPSP reductions. Similar reductions were seen in the combined presence of the GABA antagonists picrotoxin and CGP55845A, indicating a lack of involvement of GABAergic mechanisms in the action of L-AP4. Pairing of optic tract stimuli (20 ms separation) resulted in paired-pulse depression at all ages. L-AP4 was found to reduce paired-pulse depression at both 10 microM and 100 microM in slices from all ages of rat. The results of this study suggest that mGlu4/mGlu8 and mGlu7 receptors modulate retino-tectal transmission via a presynaptic mechanism, and that these effects are greatest in young animals. This is the first demonstration of a functional change in Group III receptor effect with aging, and this would be consistent with developmental regulation of these receptors.

Age Factors↗
PubMed2005

Recruitment of local excitatory circuits in the superior colliculus following deafferentation and the regeneration of retinocollicular inputs.

The local synaptic connectivity in the superficial gray layer of the superior colliculus (SC) was assessed following retinal ganglion cell axonal regeneration through a peripheral nerve graft into the SC of Lister Hooded rats, using in vitro brain slice techniques. Repair was effected between the ipsilateral eye and SC, following bilateral lesion of optic nerves and ablation of ipsilateral occipital cortex. Deafferentation surgery alone resulted in a complete loss of synaptic potentials of extrinsic origin, once both retinal and cortical inputs were removed. Stimulation of graft insertion sites elicited synaptic responses comprising monosynaptic and network-mediated depolarising events. This activity, together with similar spontaneous bursts of depolarising events and action potential firing, was generated by the activation of non-N-methyl-D-aspartate glutamate receptors. This behaviour may reflect the development of a local recurrent synaptic connectivity following the repair surgery, as both evoked and spontaneous responses developed into large long-lasting bursts of excitatory activity when inhibition mediated by GABA receptors was blocked. These results suggest that the ultrastructural changes in the superficial layers of the SC resulting from deafferentation are reflected functionally at the synaptic level in the target structure even after repair. Such changes are likely to compromise the ability of the target structure to function normally during information processing. Therefore, although axons regenerating along peripheral nerve grafts can make functional synaptic connections, their efficacy in activating the target structure will probably be compromised by local changes in synaptic connectivity.

Action Potentials↗
PubMed2004

Improvement of neuronal visual responses in the superior colliculus in Prph2(Rd2/Rd2) mice following gene therapy.

Inherited retinal degenerations are a major cause of blindness for which there are currently no effective therapies. Significant progress concerning in vivo gene transfer has allowed retardation of degeneration or retinal functional improvement in different animal models. To date, there has been no evaluation of the impact of these treatments on higher visual function, a critical step for validating gene therapy treatment strategies. Here, we have used adeno-associated (AAV2)-mediated gene transfer of Prph2 in the Prph2(Rd2/Rd2) mouse model. We then assessed higher visual function by recording from central visually responsive neurons in the superior colliculus and improvements were correlated in individual animals with retinal function (ERG) and histological and biochemical changes. Although gene replacement therapy only partially restores photoreceptor morphology, it results in a 300% increase of the visual cycle protein rhodopsin, leading to retinal function improvement (250% increase of b-wave amplitude) and significantly higher central visual responses (166% increase at 24 cd/m(2)). These findings suggest that gene replacement therapy leading to even relatively modest structural improvement may result in improved central visual function.

Action Potentials↗
PubMed2004

Activation of Group II and Group III metabotropic glutamate receptors by endogenous ligand(s) and the modulation of synaptic transmission in the superficial superior colliculus.

Previous work from this laboratory indicates that Group II/III metabotropic glutamate (mGlu) receptors modulate responses of SC neurones to visual stimuli in vivo. It is thought that tonic levels of glutamate may be sufficient to activate some mGlu receptors. We wished to investigate if these receptors are activated under ambient conditions in SC. Field excitatory postsynaptic potentials (fEPSPs) evoked by optic tract stimulation were recorded from 300 microm slices of the adult pigmented rat superior colliculus at 34 degrees C. The Group II receptor selective agonist LY354740 (100-300 nM) had no significant effect on the peak amplitude of the fEPSP, although it did enhance the late phase of the fEPSP. In order to test for activation of Group II receptors by endogenous ligand, the selective antagonists LY341495 (50 nM) or EGLU (200 microM) were applied: these either enhanced or reduced the fEPSP amplitude. In similar experiments carried out at 22 degrees C, no effect was seen. The fEPSP enhancements, but not the fEPSP reductions, could be occluded by GABA antagonists. Application of higher concentrations of LY341495 (300, 600 nM-known to also affect Group III receptors, particularly mGlu8), or co-application of 50 nM LY341495 and the Group III-selective antagonist CPPG (100 microM) produced enhancements of responses, or counteracted response reductions over those seen with 50 nM LY341495 alone. The predominant Group II receptor in SC is mGlu3. It is known that this can be located presynaptically on GABAergic and glutamatergic terminals, postsynaptically, and on glia. Our results indicate that such receptors are tonically activated by endogenous transmitter, have distinct effects, and influence retino-collicular transmission. Furthermore, there is a segregation of effects where receptors exert some of their effects via modulation of GABAergic circuitry.

Action Potentials↗
PubMed2004

Release of homocysteic acid from rat thalamus following stimulation of somatosensory afferents in vivo: feasibility of glial participation in synaptic transmission.

The sulphur-containing amino acid homocysteic acid (HCA) is present in and released in vitro from nervous tissue and is a potent neuronal excitant, predominantly activating N-methyl-d-aspartate (NMDA) receptors. However, HCA is localised not in neurones but in glial cells [Eur J Neurosci 3 (1991) 1370], and we have shown that it is released from astrocytes in culture upon glutamate receptor activation [Neuroscience 124 (2004) 377]. We now report the in vivo release of HCA from ventrobasal (VB) thalamus following natural stimulation of somatosensory afferents arising from the facial vibrissae of the rat. Simultaneously with multi-unit recording, [35S]-methionine, a HCA precursor, was perfused through a push-pull cannula in VB thalamus of anaesthetized rats. Perfusates were collected before, during and after 4 min stimulation of the vibrissal afferents with an air jet. A marked release of radiolabeled HCA was observed during and after the stimulation. Furthermore, the beta-adrenoreceptor agonist isoproterenol, which is known to evoke HCA release from glia in vitro, was found to increase the efflux of HCA in the perfusate in vivo. In separate experiments, the excitatory actions of iontophoretically applied HCA on VB neurones were inhibited by the NMDA receptor antagonist CPP, but not by the non-NMDA antagonist CNQX. These results suggest a possible "gliotransmitter" role for HCA in VB thalamus. The release of HCA from glia might exert a direct response or modulate responses to other neurotransmitters in postsynaptic neurons, thus enhancing excitatory processes.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2003

Kainate receptor (GluR5)-mediated disinhibition of responses in rat ventrobasal thalamus allows a novel sensory processing mechanism.

Kainate receptors have been studied extensively in vitro, but how they might function physiologically remains unclear. We studied kainate receptor modulation of synaptic responses in the rat ventrobasal thalamus using the novel antagonist LY382884 and the agonist ATPA (selective for GluR5-containing kainate receptors) as tools. No evidence could be found for a direct contribution of kainate receptors to responses of thalamic relay cells to lemniscal (sensory) input in thalamic slices studied with the aid of intracellular and field potential recordings, using selective AMPA and NMDA receptor antagonists and LY382884. However, the GluR5 agonist ATPA reduced the IPSPs originating from the thalamic reticular nucleus. Extracellular single-neurone recordings in anaesthetised rats showed that excitatory responses evoked by physiological vibrissa afferent stimulation were reduced by LY382884 applied iontophoretically at the recording site. This action of the antagonist was occluded when GABA receptors were blocked, indicating that the reduction in excitatory sensory responses by LY382884 is due to an action on GABAergic inhibition arising from the thalamic reticular nucleus. Further experiments showed that these actions depended on whether inhibition was evoked during activation of the excitatory receptive field rather than when inhibition was evoked from a surround vibrissa. We suggest that GluR5 is located presynaptically on inhibitory GABAergic terminals of thalamic reticular nucleus neurones, and that it is normally activated by glutamate spillover from synapses between excitatory afferents and relay neurones during physiological stimulation. We propose that this GluR5-activated disinhibition has an important novel role in extracting sensory information from background noise.

Animals↗
PubMed2003

Group II and III metabotropic glutamate receptors and the control of the nucleus reticularis thalami input to rat thalamocortical neurones in vitro.

Intracellular recordings were made from neurones in the thalamic reticular nucleus (TRN) and ventro-basal (VB) thalamus in slices of rat midbrain in vitro. Electrical stimulation of the medial lemniscus or TRN resulted in the generation of complex synaptic potentials containing disynaptic inhibitory post-synaptic potentials (IPSPs) in VB thalamocortical neurones. Analysis of the excitatory synaptic responses in TRN neurones indicates they can produce burst output response irrespective of the level of sub-threshold membrane potential. This suggests that network-evoked IPSPs in VB thalamocortical neurones occur following a burst of TRN action potentials. Using ionotropic glutamate receptor antagonists, the activation of these disynaptic events was blocked, and the monosynaptic IPSPs that resulted from the direct activation of the TRN could be isolated. The selective Group II agonists LY354740 (1-10 microM) and N-acetyl-aspartyl-glutamate (NAAG; 100-500 microM) both caused a reversible depression of these monosynaptic TRN IPSPs without any effect on membrane potential or input resistance. Likewise, the specific Group III agonist L-2-amino-4-phosphonobutanoate (10-500 microM), but not (RS)-4-phosphonophenylglycine (1 and 30 microM) also caused a reversible depression of these IPSPs, again without any effect on membrane potential or input resistance.Thus, the IPSPs recorded in VB thalamocortical neurones, evoked by TRN activation, can be depressed by the activation of either Group II or III metabotropic glutamate receptors. This is consistent with the location of these receptor types on the presynaptic terminals of TRN axons in the VB thalamus. This raises the possibility that, during periods of intense excitatory activity, glutamate release could influence the release of GABA from TRN axon terminals in the thalamus. In addition, as NAAG is located in the axons and terminals arising from the TRN, there is the possibility that this dipeptide is also released by these terminals to control the release of GABA during periods of high activity in the TRN.

Animals↗
PubMed2002

Glutamate receptor functions in sensory relay in the thalamus.

It is known that glutamate is a major excitatory transmitter of sensory and cortical afferents to the thalamus. These actions are mediated via several distinct receptors with postsynaptic excitatory effects predominantly mediated by ionotropic receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate varieties (NMDA). However, there are also other kinds of glutamate receptor present in the thalamus, notably the metabotropic and kainate types, and these may have more complex or subtle roles in sensory transmission. This paper describes recent electrophysiological experiments done in vitro and in vivo which aim to determine how the metabotropic and kainate receptor types can influence transmission through the sensory thalamic relay. A particular focus will be how such mechanisms might operate under physiological conditions.

Afferent Pathways↗
PubMed2002

Group I metabotropic glutamate receptors (mGluRs) modulate visual responses in the superficial superior colliculus of the rat.

Group I metabotropic glutamate receptors (mGluRs) are expressed in cells in the superficial layers of the rat superior colliculus (SSC) and SSC afferents. The purpose of this study was to investigate the physiological effect of Group I mGluR activation on visual responses of SSC neurones using both in vivo and in vitro techniques. In the in vivo preparation, agonists and antagonists were applied by iontophoresis and single neurone activity was recorded extracellularly in anaesthetised rats. Application of the Group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) resulted in a reversible inhibition of the visual response. The effect of DHPG could be blocked by concurrent application of the Group I (mGluR1/mGluR5) antagonist (S)-4-carboxyphenylglycine (4CPG) or mGluR1 antagonist (+)-2-methyl-4-carboxyphenylglycine (LY367385). Application of 4CPG alone resulted in a facilitation of the visual response and this effect was not changed when the visual stimulus contrast was varied. Response habituation was observed when visual stimuli were presented at 0.5 s intervals, but this was not affected by DHPG or 4CPG. In slices of the superior colliculus, stimulation of the optic tract resulted in a field EPSP recorded from the SSC whose duration was increased in the presence of the GABA antagonists picrotoxin and CGP55845. Application of DHPG (5-100 microM) reduced the field EPSP, and this effect could be reversed by the mGluR1 antagonist LY367385 (200 microM), but not by the mGluR5 antagonist MPEP (5 microM). These data show that activation of mGluR1, but probably not mGluR5, can modulate visual responses of SSC neurones in vivo, and that this could be via presynaptic inhibition of glutamate release from either retinal or, possibly, cortical afferents.

Amino Acids↗
PubMed2002

Reduction of excitatory transmission in the retino-collicular pathway via selective activation of mGlu8 receptors by DCPG.

We have previously shown that activation of Group III metabotropic glutamate (mGlu) receptors modulates synaptic transmission in the superior colliculus. We thus investigated the effect of the selective mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) on excitatory synaptic transmission in the superficial superior colliculus (SC) using an in vitro slice preparation of the rat SC. Field EPSPs evoked by optic tract stimulation under conditions of GABA receptor blockade were reduced by DCPG by up to 67.8+/-5.46% (EC(50) 1.25+/-0.56 microM), and this effect could be antagonised by LY341495 at a concentration (300 nM) known to be effective at mGlu8 receptors but not at mGlu4 or mGlu7 receptors. The broad-spectrum (mGlu4/mGlu7/mGlu8) agonist L-2-amino-4- phosphonobutyric acid (L-AP4) produced similar reductions of synaptic transmission (maximal reduction 68.6+/-2.33%; EC(50) 5.7+/-2.61 microM). These data are consistent with previous results which show that mGlu8 receptor activation can reduce synaptic transmission in the spinal cord, and indicate that similar mechanisms operate in other brain areas. Furthermore, this indicates that the mGlu8 receptor may have a role in the modulation of visual transmission in the superior colliculus.

Animals↗
PubMed2002

Distribution of metabotropic glutamate receptors in the superior colliculus of the adult rat, ferret and cat.

The distribution of different metabotropic glutamate receptors (mGluRs 1a, 1b, 1c, 2/3, 4 and 5) has been compared in the superior colliculus of the rat, cat and ferret using immunohistochemical techniques and light microscopy. We found that although there are differences in labelling patterns between the species, there are also substantial similarities. In general, there was only light staining for the various mGluR1 splice variants, whereas labelling for the other Group I receptor, mGluR5, was heavier and with a pattern which suggested that at least some label arose from retinal afferents to the superficial superior colliculus. A further consistent feature in all species was labelling of astrocytes in the optic nerve/optic tract, superficial superior colliculus and brain at the collicular level with the antibody directed towards the Group II receptors, mGluR2 and mGluR3. Staining for the Group III receptor, mGluR4, was dense in the superficial superior colliculus in all species, with characteristics suggesting nerve fibre staining. mGluR4 staining was seen in the cat optic nerve/optic tract. One source of mGluR4 staining in the superior colliculus may thus be retinal axons, although other sources cannot be entirely excluded. These results demonstrate that distributions of mGluRs in these species have significant similarities but also some differences, suggesting that within the superior colliculus there may be some preservation of functional roles for some of the different receptor types. This is particularly so for the Group II and Group III receptors, which appear to have specific and distinct roles in the modulation of visual responses.

Animals↗
PubMed2002

Glial-neuronal transfer of arginine and S-nitrosothiols in nitric oxide transmission.

The arginine-nitric oxide (Arg-NO) and the S-nitrosothiols systems, two less well-studied aspects of NO transmission in the central nervous system, are reviewed. A growing body of evidence suggested that they play a crucial role in NO synthesis and activity. l-Arginine, the NO precursor, is predominantly localized in glia. Together with in vitro and in vivo results of arginine release, this suggests a transfer of arginine from glia to neurons in order to supply NO synthase with its substrate. NO biosynthesis may thus involve the co-occurrence of the glial-neuronal transfer of arginine and of NOS activation. The arginine availability may shed light on the dual, beneficial and toxic effects of NO. At low arginine concentrations, neuronal NO synthase generates NO and superoxide, favouring the production of the toxin peroxynitrite. NMDA-induced excitotoxicity in neuronal cells is dependent on arginine availability and glia may play a neuroprotective role by supplying arginine. The reversible S-nitros(yl)ation of thiol containing molecules may represent an important cellular signal transduction mechanism, probably comparable to phosphorylation. S-nitrosothiols, in particular through the presence and release of S-nitroso-cysteinylglycine in sensory thalamus, may act as a local buffering system in NO transmission. This may represent a novel specific facilitating mechanism in order to enhance transmission of persistent stimuli.

Animals↗
PubMed2001

Group II and III metabotropic glutamate receptors contribute to different aspects of visual response processing in the rat superior colliculus.

1. Neurones in the superior colliculus (SC) respond to novel sensory stimuli and response habituation is a key feature of this. It is known that both ionotropic and metabotropic glutamate (mGlu) receptors participate in visual responses of superficial SC neurones. A feature of Group II and Group III mGlu receptors is that they may modulate specific neural pathways, possibly via presynaptic mechanisms. However, less is known about how this may relate to functions of systems in whole animals. We have therefore investigated whether these receptors affect specific attributes of visual responses in the superficial SC. 2. Recordings were made from visually responsive neurones in anaesthetised rats, and agonists and antagonists of Group II and III mGlu receptors were applied iontophoretically at the recording site. 3. We found that application of the Group III metabotropic glutamate receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4) produced an increase in visual response habituation, whilst Group III antagonists decreased habituation. These effects were independent of the response habituation mediated via GABA(B) receptors. In contrast, modulation of Group II mGlu receptors with the specific agonist LY354740 or the antagonist LY341495 did not affect response habituation, although these compounds did modulate visual responses. This suggests a specific role for Group III mGlu receptors in visual response habituation. 4. The magnitude of Group II effects was smaller during presentation of low contrast stimuli compared with high contrast stimuli. This suggests that activation of Group II receptors may be activity dependent and that these receptors can translate this into a functional effect in adapting to high contrast stimuli.

Amino Acids↗
PubMed2001

Actions of the systemically active metabotropic glutamate antagonist MPEP on sensory responses of thalamic neurones.

It is known that metabotropic glutamate receptors of the subtypes mGlu1 and mGlu5 participate in nociceptive processing in the thalamus, an area of prime importance in supra-spinal sensory processing. Antagonists of these receptors thus have potential as centrally-acting analgesics. We have investigated whether intravenous administration of the novel mGlu5-receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) is able to reduce nociceptive responses of thalamic neurones. Extracellular recordings were made from single thalamic neurones of adult male Wistar rats anaesthetised with urethane. MPEP (1 mg/kg) reduced neuronal responses to noxious thermal stimuli to a mean of 24+/-4% of control within 10 min, whereas saline injections had no significant effect. Partial recovery was seen within 30-45 min after injection. Responses of neurones to non-noxious stimuli were not significantly affected by MPEP administration. In addition, MPEP caused an increase in the power of the slow-wave component (<1 Hz) of the electroencephalogram (EEG), but had no significant effect on peak frequency of the EEG or on heart rate. These results confirm that nociceptive responses of thalamic neurones are mediated in part by mGlu5 receptors. Furthermore, the effectiveness of intravenous MPEP suggests that such antagonists may be useful as centrally-acting analgesics.

Action Potentials↗