S. Liachenko et al., COMPARISON OF ANESTHETIC AND NON-ANESTHETIC EFFECTS ON DEPOLARIZATION-EVOKED GLUTAMATE AND GABA RELEASE FROM MOUSE CEREBROCORTICAL SLICES, British Journal of Pharmacology, 123(6), 1998, pp. 1274-1280
1 Investigation with substances that are similar in structure, but dif
ferent 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-triflu
orocyclobutane (F3), and the non-anaesthetic, 1,2-dichlorohexafluorocy
clobutane (F6), on K+-evoked glutamate and gamma-aminobutyric acid (GA
BA) release from isolated, superfused, cerebrocortical slices from mic
e, by use of h.p.l.c. with fluorescence detection for quantitative ana
lysis. 3 At clinically relevant concentrations, the anaesthetic, F3, i
nhibited 40 mM K+-evoked glutamate and GABA release by 72% and 47%, re
spectively, whereas the structurally similar non-anaesthetic, F6, supp
ressed 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, s
uggesting that F3 and F6 did not cause any non-specific or irreversibl
e changes in the brain slices. 4 Our findings suggest that suppression
of excitatory neurotransmitter release may not be directly relevant t
o the primary action of general anaesthetics. A mechanism involving in
hibitory postsynaptic action is implicated, in which a moderate suppre
ssion of depolarization-evoked GABA release by the anaesthetic may be
consistent with the enhancement of postsynaptic GABAergic activities.