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

Abstract

1 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. 2 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. 3 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. 4 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. 5 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). 6 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. 7 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. 8 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.