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 action; for some agents multiple receptors-ion channels may be implicated. 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 integrated portion of the central nervous system involve multiple actions at glutamate non-NMDA, glutamate NMDA, and GABA(A) receptors. The effects of ketamine 1-50 mu mol litre(-1) were examined on three pharmacologically distinct responses in isolated superfused neonatal rat spinal cord: the monosynaptic reflex (glutamate non-NMDA); a slow ventral root potential (VRP) with a large NMDA-mediated component; and the dorsal root potential (DRP) (GABA(A)). Ketamine, at concentrations relevant to anaesthesia (1-50 mu mol litre(-1)), reversibly depressed the area under the curve of the slow VRP in a concentration-dependent fashion. The effects of ketamine were selective for the early (0-1 s) component of the slow VRP. The monosynaptic reflex was unaffected at these concentrations. The actions of ketamine resembled those of the NMDA antagonist APV. Dorsal root potentials evoked by dorsal root stimulation or by muscimol were either unaffected or reversibly depressed by ketamine 1-20 mu mol litre(-1). The concentrations tested include the anaesthetic range for both rats and humans. The effects of ketamine on neurotransmission in this preparation can be accounted for entirely by its action at NMDA receptors. Glutamate non-NMDA receptors were unaffected and GABA(A) transmission was not enhanced. Ketamine, therefore, has effects which appear to result from actions on one receptor subtype. Other anaesthetic agents act on other receptors and may either be specific to one type or exert their effects via multiple actions on several different receptors.