Salt TE; Binns KE; (2000) Contributions of mGlu1 and mGlu5 receptors to interactions with N-methyl-D-aspartate  receptor-mediated responses and nociceptive sensory responses of rat thalamic neurones. Neuroscience, 100: 375-380.

Previous work from this laboratory has shown that nociceptive responses of rat ventrobasal thalamus neurones can be reduced by N-methyl-D-aspartate (NMDA) antagonists and by selective metabotropic glutamate receptor mGlu1 antagonists. The recent development of the mGlu5-selective antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) now allows the direct probing of possible mGlu5 involvement in thalamic nociceptive responses. Extracellular recordings were made from single neurones in the ventrobasal thalamus and immediately overlying dorsal thalamic nuclei of adult urethane-anaesthetised rats using multi-barrel electrodes. Responses of neurones to iontophoretic applications of the mGlu5-selective agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG) were selectively reduced during continuous iontophoretic applications of MPEP. Similar applications of MPEP reduced neuronal responses to noxious thermal stimuli to 53±9.5 % of control responses. Co-application by iontophoresis of NMDA and metabotropic glutamate receptor agonists resulted in a mutual potentiation of excitatory responses. This effect could be reduced by either MPEP or the mGlu1 antagonist LY367385. These results, taken together with previous data, suggest that acute thalamic nociceptive responses are mediated by a combination of mGlu1, mGlu5 and NMDA receptor activation, and that co-activation of these receptors produces a synergistic excitatory effect. Thus blockade of any of these receptor types would have a profound effect on the overall nociceptive response.

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