The interaction between ethanol and cysteine on the central depressant effects of ethanol in mice

In this study male Swiss-Webster mice were used to examine the effects of cysteine (ICV), a precursor in the biosynthesis of taurine, on ethanol-induced loss of the righting reflex. The interaction of ethanol with gamma-aminobutyric acid (GABA) and isethionic acid, a metabolite of taurine, was also investigated on ethanol-induced central nervous system depression as measured by loss of the righting reflex experiments. Immediately after the animals regained the righting reflex following ethanol injection (IP) mice received an ICV injection of saline, cysteine (1, 15 or 25 μmol/kg), GABA (1, 15 or 25 μmol/kg) or isethionic acid (25 or 50 μmol/kg). Upon ICV administration of cysteine or GABA the mice again lost the righting reflex. This effect occurred immediately and in a dose-dependent manner. The compound, isethionic acid, failed to cause a second loss of the righting reflex following ethanol administration (IP). In the absence of ethanol cysteine or GABA (25 μmol/kg, ICV) did not produce a substantial loss of the righting reflex in mice. In another experiment mice were pretreated (IP) with L-2-oxothiazolide-4-carboxylate (OTC) 2 hr prior to ethanol administration (IP). OTC is a compound which can be converted to cysteine in the body. In the presence of ethanol OTC (15 mmol/kg) caused an enhancement of ethanol-induced central nervous system depression under certain conditions. When OTC (25 μmol/kg), however, was injected by the ICV route immediately after the animals regained the righting reflex following ethanol administration, OTC did not augment the central depressant properties of ethanol. This experiment indicated that OTC was inactive by itself and that it required a certain time period to be converted to cysteine in mice. In this investigation the results suggest that cysteine, a sulfur-containing amino acid, can enhance ethanol-induced depression as measured by the loss of the righting reflex and that cystein may be involved in some manner with the central depressant properties of ethanol.