Effects of neurotropic drugs on sodium influx into rat brain cortex in vitro

Abstract

Two methods have been adopted for studying the effects of neurotropic drugs on sodium ion influx into rat brain cortex slices incubated aerobically in a physiological saline-glucose medium: (a) a direct method in which the influx of 22Na + from the incubation medium is measured: (b) an indirect method in which the rate of [1- 14C] acetate oxidation to 14CO 2 is measured. The latter process is inhibited by sodium ions and stimulated by potassium ions. The results of both methods show that the local anesthetics (cocaine 0·2 mM lidocaine 0·5 mM and 1 mM and procaine 1 and 3 mM) block the increased influx of Na + due to electrical stimulation without affecting the content of 22Na + found in the brain tissue in the unstimulated state. Tetrodotoxin (1 μm), chlorpromazine (0·1 mM) and atropine (5 mM) behave similarly. Chlorpromazine at a higher concentration (0·5 mM) causes increased influx of 22Na + into the brain slices in the unstimulated state and this is correlated with its marked inhibition, at this concentration, of the activity of membrane Na +-K +-ATPase (as occurs also with ouabain 10 μm). The local anesthetics at the concentrations quoted do not affect membrane Na +-K +-ATPase. The barbiturates investigated (amytal 0·25 and 0·5 mM and pentothal 0·1 and 0·2 mM) do not abolish the influx of Na + following electrical stimulation and there is no evidence from the results of these experiments that the barbiturates, at the concentrations quoted, affect the movements of sodium or potassium ions across the brain cell membrane. In contrast, also, with the effects of local anesthetics, the barbiturates inhibit the oxidation of [1- 14C]acetate to 14CO 2 without markedly influencing the effects of potassium ions or of electrical stimulation on this process. The effects of barbiturates may be explained by their inhibitory action on brain cell energetics.