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 γ‐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 m M 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 m M KCl after a ∼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.British Journal of Pharmacology (1998) 123 , 1274–1280; doi: 10.1038/sj.bjp.0701728