SELECTIVE EFFECTS OF KETAMINE ON AMINO ACID-MEDIATED PATHWAYS IN NEONATAL RAT SPINAL-CORD

Many ion channels have been proposed as target sites for anaesthetic a ction; for some agents multiple receptors-ion channels may be implicat ed. In addition to acting as a non-competitive antagonist at glutamate NMDA receptors, ketamine also affects other ion channels. The present study was undertaken to determine if the effects of ketamine in an in tegrated portion of the central nervous system involve multiple action s at glutamate non-NMDA, glutamate NMDA, and GABA(A) receptors. The ef fects of ketamine 1-50 mu mol litre(-1) were examined on three pharmac ologically distinct responses in isolated superfused neonatal rat spin al cord: the monosynaptic reflex (glutamate non-NMDA); a slow ventral root potential (VRP) with a large NMDA-mediated component; and the dor sal root potential (DRP) (GABA(A)). Ketamine, at concentrations releva nt to anaesthesia (1-50 mu mol litre(-1)), reversibly depressed the ar ea under the curve of the slow VRP in a concentration-dependent fashio n. The effects of ketamine were selective for the early (0-1 s) compon ent of the slow VRP. The monosynaptic reflex was unaffected at these c oncentrations. The actions of ketamine resembled those of the NMDA ant agonist APV. Dorsal root potentials evoked by dorsal root stimulation or by muscimol were either unaffected or reversibly depressed by ketam ine 1-20 mu mol litre(-1). The concentrations tested include the anaes thetic range for both rats and humans. The effects of ketamine on neur otransmission in this preparation can be accounted for entirely by its action at NMDA receptors. Glutamate non-NMDA receptors were unaffecte d and GABA(A) transmission was not enhanced. Ketamine, therefore, has effects which appear to result from actions on one receptor subtype. O ther anaesthetic agents act on other receptors and may either be speci fic to one type or exert their effects via multiple actions on several different receptors.