Salt TE; Turner JP; (1998) Reduction of sensory and metabotropic glutamate receptor responses in the thalamus by the novel mGluR1-selective antagonist S-2-methyl-4-carboxy-phenylglycine (LY367385). Neuroscience, 85:655-658
Previous work from this laboratory has shown that responses of thalamic neurones in vivo to the metabotropic
glutamate receptor agonists ACPD and DHPG can be reduced by a variety of phenylglycine antagonists.
Responses of thalamic neurones to noxious thermal somatosensory stimuli were reduced in parallel by these
antagonists, indicating that these responses are mediated by Group I mGluRs (i.e. mGluR1 and/or mGluR5),
which are known to be linked to phosphoinositol phosphate hydrolysis. The recent development of
LY367385 as an antagonist which is highly selective for mGluR1 compared to mGluR5 on human receptors
expressed in AV-12 cells, now offers the possibility of discriminating between these two receptor subtypes in
order to distinguish which is involved in thalamic responses. We have made recordings from single somatosensory neurones in the thalamus of the rat, and find that LY367385 is able to reduce responses of neurones to ACPD, DHPG, and noxious stimuli without significant effect on responses to either NMDA or AMPA. These results suggest that excitatory responses of thalamic neurones to ACPD and DHPG may be mediated by mGluR1. Furthermore, the reduction of nociceptive responses by LY367385 indicates that mGluR1 is involved in thalamic nociceptive processing and that such antagonists may have analgesic properties.
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