Effects of depressant amino acids and antagonists on an in vitro spinal cord preparation from the adult rat

Abstract

A mature sacrococcygeal in vitro spinal preparation from the rat has been used to demonstrate effects of neutral amino acids and their antagonists. γ-Aminobutanoate (GABA), glycine and taurine (0.5–5 mM) produced dose-dependent depression of spontaneous paroxysmal activity generated in Mg 2+-free medium. The depressant effect of GABA was antagonised selectively by picrotoxin (25–50 μM) and the depressant effects of glycine and taurine were antagonised selectively by strychnine (0.2 μM). Glycine (0.5–5 mM) had a dose-dependent depolarizing action which was present at the central ends of isolated ventral roots. γ-Aminobutanoate and taurine, had only weak depolarizing actions on ventral root fibres. Depolarizing responses to glycine showed a marked fading. Reduction in the fading appeared to be responsible for a paradoxical potentiation of glycine-induced depolarizations, which occurred in the presence of strychnine (0.2–2 μM). Strychnine (2–10 μM), picrotoxin (10–50 μM) or bicuculline (10 μM) had little or no effect on the amplitude, duration or latency of the monosynaptic component of ventral root reflexes evoked by supramaximal stimulation of dorsal roots (DR-VRP). However all three antagonists introduced slow, NMDA receptor mediated, components to these ventral root potentials. Picrotoxin and bicuculline, but not strychnine, reversibly depressed the dorsal root potential evoked from an adjacent dorsal root (DR-DRP). The depressant actions of 2-amino-5-phosphonopentanoate (AP5), kynurenate and 3-((±)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) revealed both NMDA and non-NMDA receptor mediated components in the dorsal root potential.