Contributions of mGlu1 and mGlu5 receptors to interactions with N-methyl-D-aspartate receptor-mediated responses and nociceptive sensory responses ofrat thalamic neurons

The nociceptive responses of rat ventrobasal thalamus neurons can be reduce d by N-methyl-D-aspartate antagonists and by selective metabotropic glutama te receptor mGlu1 antagonists. The recent development of the mGlu5-selectiv e antagonist 6-methyl-2-(phenylethynyl)-pyridine now allows the direct prob ing of the possible involvement of mGlu5 receptors in thalamic nociceptive responses. Extracellular recordings were made from single neurons in the ve ntrobasal thalamus and immediately overlying dorsal thalamic nuclei of adul t urethane-anaesthetized rats using multi-barrel electrodes. Responses of n eurons to iontophoretic applications of the mGlu5-selective agonist (R,S)-2 -chloro-5-hydroxyphenylglycine were selectively reduced during continuous i ontophoretic applications of 6-methyl-2-(phenylethynyl) -pyridine. Similar applications of 6-methyl-2-(phenylethynyl)pyridine reduced neuronal respons es to noxious thermal stimuli to 53 +/- 9.5% of control responses. Co- appl ication by iontophoresis of N-methyl-D-aspartate and metabotropic glutamate receptor agonists resulted in a mutual potentiation of excitatory response s. This effect could be reduced by either 6-methyl-2-(phenylethynyl)-pyridi ne or the mGlu1 antagonist LY367385. These results, taken together with previous data, suggest that acute thalam ic nociceptive responses are mediated by a combination of mGlu1, mGlu5 and N-methyl-D-aspartate receptor activation, and that co-activation of these r eceptors produces a synergistic excitatory effect. Thus blockade of any of these receptor types would have a profound effect on the overall nociceptiv e response. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights re served.