Comparison of anaesthetic and non-anaesthetic effects on depolarization-evoked glutamate and GABA release from mouse cerebrocortical slices

1 Investigation with substances that are similar in structure, but different in anaesthetic properties, may lead to further understanding of the mechanisms of general anaesthesia. 2 We have studied the effects of two cyclobutane derivatives, the anaesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F3), and the non-anaesthetic, 1,2-dichlorohexafluorocyclobutane (F6), on K+-evoked glutamate and gamma-aminobutyric acid (GABA) release from isolated, superfused, cerebrocortical slices from mice, by use of h.p.l.c. with fluorescence detection for quantitative analysis. 3 At clinically relevant concentrations, the anaesthetic, F3, inhibited 40 mM K+-evoked glutamate and GABA release by 72% and 47%, respectively, whereas the structurally similar non-anaesthetic, F6, suppressed evoked glutamate release by 70% but had no significant effects on evoked GABA release. A second exposure to 40 mM KCl after a similar to 30 min washout of F3 or F6 showed recovery of K+-evoked release, suggesting that F3 and F6 did not cause any non-specific or irreversible changes in the brain slices. 4 Our findings suggest that suppression of excitatory neurotransmitter release may not be directly relevant to the primary action of general anaesthetics. A mechanism involving inhibitory postsynaptic action is implicated, in which a moderate suppression of depolarization-evoked GABA release by the anaesthetic may be consistent with the enhancement of postsynaptic GABAergic activities.