Participation of NMDA and non-NMDA excitatory amino acid receptors in the mediation of spinal reflex potentials in rats: an in vivo study.

1. The effect of various intravenously administered excitatory amino acid (EAA) antagonists on the dorsal root stimulation-evoked, short latency (up to 10 ms) spinal root reflex potentials of chloralose-urethane anaesthetized C1 spinal rats was studied, in order to gain information on the involvement of non-NMDA (AMPA/kainate; AMPA = alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) and NMDA (N-methyl-D-aspartate) receptors in their mediation. The competitive non-NMDA antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX; 1-32 mg kg-1), the non-competitive non-NMDA antagonist, 1-(amino)phenyl-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine (GYKI 52466; 0.5-8 mg kg-1), the competitive NMDA antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP, 2-8 mg kg-1) and two non-competitive NMDA antagonists: MK-801 (0.5-2 mg kg-1) and ketamine (2-32 mg kg-1) were used as pharmacological tools. 2. Validating the applied pharmacological tools regarding selectivity at the applied doses, their effects were tested on direct (electrical) as well as on synaptic excitability of motoneurones evoked by intraspinal stimulation. Furthermore, their effect was investigated on the responses elicited by microiontophoretic application of EAA agonists (AMPA, kainate and NMDA) into the motoneurone pool, where the extracellular field potential evoked by antidromic stimulation of the ventral root was recorded to detect the effects of EAA agonists. 3. NBQX and GYKI 52466 were able to abolish completely the mono-, di- and polysynaptic ventral root reflexes (MSR, DSR, PSR) and the synaptic excitability of motoneurones, while hardly influencing direct excitability of motoneurones. They markedly attenuated AMPA and kainate responses whilst having little or no effect on NMDA responses. 4. Apparently 'supramaximal' doses of CPP and MK-801 slightly inhibited MSR (by about 10%) moderately reduced DSR and PSR (by about 20-30%) and did not influence excitability of motoneurones. They selectively blocked responses to NMDA. 5. Ketamine dose-dependently inhibited MSR, DSR and PSR. Nevertheless, diminution of none of the responses exceeded 50%. It reduced both direct and synaptic excitability of motoneurones, thus displaying a local anaesthetic-like effect, which may contribute to its reflex inhibitory action. It depressed responses to NMDA whilst having negligible effects on responses to AMPA and kainate. 6. We conclude that non-NMDA receptors play a substantial role in the mediation of MSR, DSR and PSR, while NMDA receptors contribute little to this. Neither MSR nor PSR is mediated exclusively by non-NMDA or NMDA receptors, respectively. 7. The drugs investigated in this study, with the exception of ketamine, proved to be useful tools for elucidation of the involvement of EAA receptors in various processes in vivo Keywords: Glutamate receptors; AMPA; kainate; NMDA; NBQX; GYKI 52466; CPP; MK-801; spinal reflex; spinal cord