Dual modulation of excitatory synaptic transmission by agonists at group Imetabotropic glutamate receptors in the rat spinal dorsal horn

The effects of group I metabotropic glutamate (mGlu) receptors on excitator y transmission in the rat dorsal horn, hut mostly substantia gelatinosa, ne urons were investigated using conventional intracellular recording in slice s. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3 -dicarboxylic acid (1S,3R-ACPD), the group I mGlu receptor selective agonis t CS)-3,5-dihydroxyphenylglycine (DHPG), and the selective mGlu subtype 5 a gonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), all induce longlasting depression of A primary afferent fibers-mediated monosynaptic excitatory po stsynaptic potential (EPSP), and long-lasting potentiation of polysynaptic EPSP, and EPSP in cells receiving C-afferent fiber input. The DHPG potentia tion of polysynaptic EPSP was partially or fully reversed by (S)-4-carboryp henylglycine (S-4CPG), the mGlu subtype 1 preferring antagonist. 2-Methyl-6 -(phenylethynyl)-pyridine, the potent and selective mGlu subtype 5 antagoni st, partially reversed the CHPG potentiation of polysynaptic EPSP. The effe cts of DHPG on monosynaptic and polysynaptic EPSPs were reduced, or abolish ed, by the N-methyl-D-aspartate (NMDA) receptor antagonist D(-)-2-amino-5-p hosphonopentanoic acid (APS). A clear and pronounced facilitation of the ex pression of DHPG- and CHPG-induced enhancement of polysynaptic EPSP, and EP SP evoked at C-fiber strength, was seen in the absence of gamma-aminobutyri c acid subtype A receptor- and glycine-mediated synaptic inhibition. Beside s dual modulation of excitatory synaptic transmission, DHPG induces depress ion of inhibitory postsynaptic potentials evoked by primary afferent stimul ation in dorsal horn neurons. In addition, group I mGlu receptor agonists p roduced a direct persistent excitatory postsynaptic effect consisting of a slow membrane depolarization, an increase in input resistance, and an inten se neuronal discharge. Cyclothiazide and (S)-4-CPG, the mGlu receptor subty pe 1 preferring antagonists, significantly attenuated the DHPG-induced depo larization. These results demonstrate that the pharmacological activation o f group I metabotropic glutamate receptors induces long-term depression (LT D) and long-term potentiation (LTP) of synaptic transmission in the spinal dorsal horn. These types of long-term synaptic plasticity may play a functi onal role in the generation of post-injury hypersensitivity (LTP) or antino ciception (LTD). (C) 2000 Elsevier Science B.V. All rights reserved.