Effects of the anaesthetic 2,6‐diisopropylphenol on synaptic transmission in the rat olfactory cortex slice

Abstract

The effects of the general anaesthetic 2,6‐diisopropylphenol (DIP) on synaptic transmission and the actions of amino acid transmitter candidates have been investigated in rat olfactory cortex slices. On electrical stimulation of the lateral olfactory tract (LOT), DIP (20 to 200 μm) increased the area of those surface field potentials which reflect γ‐aminobutyric acid (GABA)‐mediated transmission in a concentration‐dependent manner in 6 out of 12 slices. In a series of conditioning experiments, DIP (50 μm) also potentiated GABA‐mediated pre‐ and post‐synaptic inhibition. Perfusion of slices with DIP (50 μm) potentiated the reduction in the excitability of the terminals of the LOT produced by exogenous GABA in a picrotoxin‐sensitive manner. DIP (50μm) markedly potentiated the surface depolarizations evoked by GABA, muscimol and 3‐aminopropanesulphonic acid. The effect on the response to 3‐aminopropanesulphonic acid was observed over a concentration range of DIP of 6.25 to 50μm and was not blocked by the benzodiazepine receptor antagonist Ro 15–1788. In slices in which GABA‐mediated transmission was abolished by picrotoxin (25 μm), DIP (50 μm) had no significant effect on monosynaptically‐evoked excitatory transmission but depressed the areas of those field potentials which reflect di‐/polysynaptic excitations in a concentration‐dependent manner (from between 1.6 and 6.25 to 50 μm). In a series of conditioning experiments DIP (50 μm) abolished the increase in the excitability of the pyramidal cells evoked on stimulation of deep association fibres. DIP (50μm) had no significant effect on surface depolarizations evoked by N‐methyl‐d‐aspartate, quisqualate and kainate or by the transmitter candidates l‐glutamate and l‐aspartate. It is concluded that, at clinically relevant concentrations, DIP potentiates GABA‐mediated transmission probably by an interaction with the GABA receptor complex and inhibits di‐/polysynaptic excitations, possibly by inhibiting the release of excitatory transmitters. 1988 British Pharmacological Society