Counteracting roles of metabotropic glutamate receptor subtypes 1 and 5 in regulation of pain-related spatial and temporal synaptic plasticity in rat entorhinal–hippocampal pathways

2012 
Abstract It was previously found that persistent inflammatory pain state resulted in enhancement of synaptic connections and efficacy in direct entorhinal–hippocampal (EC-HIP) pathways. In the current study, the roles of two subtypes of group I metabotropic glutamate receptors in the above processes were evaluated. Similarly, pain-related spatial and temporal synaptic enhancement model was stably achieved by the multi-electrode array (8 × 8) recordings in the hippocampal slices of rats pre-treated with intraplantar (i.pl.) bee venom (BV) injection. I.pl. saline injection was used as control. Inhibition of mGluR1 by a selective antagonist 7-hydroxyiminocyclopropan [b] chromen-1α-carboxylic acid ethyl ester (CPCCOEt) resulted in a dramatic increase in synaptic connections in the hippocampal slices of rats treated by BV, but not by saline. However, inhibition of mGluR5 by a selective antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) produced no spatial change from either of the two groups. Temporally, the BV-enhanced LTP could be further incremented by antagonism of mGluR1 with CPCCOEt perfusion when plateau LTP was well established. However, the BV-enhanced LTP was significantly suppressed by antagonism of mGluR5 with MPEP. Neither of the two drugs affected magnitude of LTP in rats treated by i.pl. saline. Taken together with our previous results, it is suggested that mGluR1 be involved in tonic inhibition of EC-HIP synaptic enhancement, while mGluR5 be involved in maintenance of persistent inflammatory pain-associated EC-HIP synaptic enhancement that is largely based upon activation of ionic glutamate receptors.
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